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136 results on '"Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]"'

1. HCV-related lymphoproliferative disorders in the direct-acting antiviral era: From mixed cryoglobulinaemia to B-cell lymphoma

Author: Matheus Vieira, Cloé Comarmond, D. Saadoun, Paul Régnier, Patrice Cacoub, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP]
Subjects: Lymphoma, B-Cell, Hepatitis C virus, Lymphoproliferative disorders, lymphoma, Hepacivirus, medicine.disease_cause, Antiviral Agents, cryoglobulinemia, vasculitis, extrahepatic manifestation, 03 medical and health sciences, 0302 clinical medicine, HCV (Hepatitis C), hemic and lymphatic diseases, medicine, Humans, B-cell lymphoma, Cryoglobulinemic vasculitis, B cell, 030304 developmental biology, 0303 health sciences, treatment, Hepatology, business.industry, medicine.disease, Cryoglobulinemia, Lymphoproliferative Disorders, 3. Good health, Lymphoma, direct acting-antivirals (DAA), medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, lymphoproliferative disorder, Vasculitis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Hepatitis C virus (HCV) has been shown to induce many B-cell lymphoproliferative disorders. B lymphocytes are specialized in producing immunoglobulins, and within chronic HCV infection they can cause a range that goes from polyclonal hypergammaglobulinemia without clinical repercussions, passing by mixed cryoglobulinemic vasculitis and eventually reaching B-cell non-Hodgkin lymphoma. This spectrum is supported by substantial epidemiological, pathophysiological and therapeutic data. Many, although not all, pathogenic pathways leading from one extreme to another have been decrypted. Chronic viral antigen stimulation of B lymphocytes has a central role until the last steps towards overt malignancy. This has direct implications in treatment strategies, which always include the use of direct-acting antiviral agents sometimes associated with immunosuppressants. The role of direct-acting antiviral agents has been well established in patients with cryoglobulinemia vasculitis. Its positive impact on B cell non-Hodgkin lymphoma needs to be confirmed in larger studies with longer follow-up.
Published: 2022

2. Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

Author: Franck Phan, Samia Boussouar, Olivier Lucidarme, Mohamed Zarai, Joe-Elie Salem, Nadjia Kachenoura, Khaoula Bouazizi, Etienne Charpentier, Yasmine Niati, Hasnae Bekkaoui, Zahir Amoura, Alexis Mathian, Olivier Benveniste, Patrice Cacoub, Yves Allenbach, David Saadoun, Jean-Marc Lacorte, Salma Fourati, Suzanne Laroche, Agnes Hartemann, Olivier Bourron, Fabrizio Andreelli, Alban Redheuil, COVID-19 APHP.SU Group, Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), HAL-SU, Gestionnaire, Service de diabétologie [CHU Pitié-Salpétrière], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030204 cardiovascular system & hematology, Severity of Illness Index, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mass index, 030212 general & internal medicine, Hospital Mortality, Original Investigation, Outcome, 2. Zero hunger, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cardiac adipose tissue, Diabetes, Heart, Organ Size, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, Intensive Care Units, Adipose Tissue, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Median body, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Cardiac computed tomography, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Intensive care, Severity of illness, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Angiology, Aged, Inflammation, business.industry, SARS-CoV-2, Interleukin-6, Myocardium, COVID-19, medicine.disease, Obesity, Diabetes Mellitus, Type 2, RC666-701, business, Tomography, X-Ray Computed
Abstract: BackgroundCOVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission.MethodsEighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined.ResultsOf the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2[IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2,p p = 0.01; OR = 4.86,p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p ConclusionsCardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission,a fortioriassociated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.
Published: 2021

3. The Exostosin Immunohistochemical Status Differentiates Lupus Membranous Nephropathy Subsets With Different Outcomes

Author: Xavier Belenfant, Philippe Rouvier, Pierre Ronco, Isabelle Brocheriou, Emmanuel Esteve, Michèle Saïdi, David Buob, Tim Ulinski, Sophie Tuffet, Hanna Debiec, Zahir Amoura, Makoto Miyara, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Service de néphrologie et pédiatrie générale [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Trousseau [APHP], HAL-SU, Gestionnaire, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP]
Subjects: Pathology, medicine.medical_specialty, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, renal biopsy, systemic lupus erythematosus, Membranous nephropathy, Research Letter, medicine, skin and connective tissue diseases, 030304 developmental biology, 0303 health sciences, Systemic lupus erythematosus, medicine.diagnostic_test, business.industry, membranous nephropathy, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Nephrology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, exostosin, immunohistochemistry, Immunohistochemistry, Renal biopsy, business
Abstract: International audience; Exostosin (EXT) 1 and EXT2 proteins are recently discovered major components of the subepithelial deposits in a subset of patients with membranous nephropathy (MN).1,2 Although the detection of EXT1/2 seems to be a distinctive feature of MN related to systemic lupus erythematosus (SLE),1 the exact frequency of EXT-positive, SLE-associated MN (SLE-MN) and its potential clinical significance are not well determined.Here, we retrospectively evaluated 86 consecutive patients with biopsy-proven pure class 5 SLE-MN diagnosed between January 2010 and December 2018 in 2 nephropathology centers (La Pitié Salpêtrière and Tenon hospitals) in Paris, France; mixed classes (3 + 5 and 4 + 5 of the 2003 ISN/Renal Pathology Society classification)3 were excluded.
Published: 2021

4. Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients

Author: Maddalena Larosa, Veronique Le Guern, Nathalie Morel, Mériem Belhocine, Amelia Ruffatti, Nicolas Martin-Silva, Romain Paule, Luc Mouthon, Michel Dreyfus, Jean-Charles Piette, Odile Souchaud-Debouverie, Catherine Deneux-Tharaux, Gaelle Guettrot-Imbert, Vassilis Tsatsaris, Emmanuelle Pannier-Metzger, Anne Murarasu, Andrea Doria, Nathalie Costedoat-Chalumeau, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universita degli Studi di Padova, Université de Montréal (UdeM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Università degli Studi di Padova = University of Padua (Unipd), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, Severe preeclampsia, Classification criteria, Placenta, [SDV]Life Sciences [q-bio], Antiphospholipid syndrome, Pregnancy, Systemic lupus erythematosus, Thrombosis, Infant, Newborn, Infant, Diseases of the musculoskeletal system, 3. Good health, [SDV] Life Sciences [q-bio], Italy, Pre-Eclampsia, RC925-935, Humans, Female, Child, Research Article, Retrospective Studies
Abstract: Background The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS. Methods We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks’ gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit. Results The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus. Conclusions Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02518-7.
Published: 2021

5. Impact of hydroxychloroquine used as DMARD on SARS-CoV-2 tests and infection evolution in a population of 871 patients with inflammatory rheumatic and musculoskeletal diseases

Author: Aurélia Lanteri, Yannick Dieudonné, Mathilde Devaux, Emmanuelle Dernis, Marc André, Thomas Barnetche, Patrice Cacoub, Mathilde Roumier, Elodie Drumez, Ludovic Trefond, Olivier Aumaître, Viviane Queyrel, Isabelle Melki, Raphaèle Seror, Thierry Thomas, Eric Hachulla, Soumaya El Mahou, Christophe Richez, Nathalie Costedoat-Chalumeau, Alexandre Belot, Jean Schmidt, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Référence des Maladies auto-immunes systémiques rares d'Ile-de-Frances [Hopital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service d'Immunologie Clinique et de Médecine Interne [HUS], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre de Référence National des Maladies Auto-Immunes Systémique Rares, CHU Strasbourg, Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Service d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], CHU Necker - Enfants Malades [AP-HP], Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), AP-HP Hôpital universitaire Robert-Debré [Paris], Service Rhumatologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de compétence des maladies auto-immunes systémiques rares, Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Service de Médecine Interne [CHU Amiens-Picardie], CHU Amiens-Picardie, Réseau d'Epidémiologie Clinique International Francophone [Amiens] (RECIF Amiens), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Service de Rhumatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Hôpital Femme Mère Enfant, HCL] (RAISE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine Interne et Immunologie Clinique [Hôpital Claude Huriez, LillI, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de Rhumatologie [Saint-Etienne], CHU Saint-Etienne-Hôpital de Bellevue, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP]
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS COV-2 evolution, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Article, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, SARS CoV-2 tests, Medicine, Humans, 030212 general & internal medicine, Musculoskeletal Diseases, education, ComputingMilieux_MISCELLANEOUS, Inflammatory rheumatic and musculoskeletal diseases, 030203 arthritis & rheumatology, education.field_of_study, business.industry, SARS-CoV-2, COVID-19, Hydroxychloroquine, Virology, 3. Good health, COVID-19 Drug Treatment, DMARD, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Antirheumatic Agents, business, medicine.drug
Abstract: International audience
Published: 2021

6. Exposure to inorganic particles in paediatric sarcoidosis: the PEDIASARC study

Author: Véronique Houdouin, Catherine Cavalin, Antoine Deschildre, Jean-Marc Naccache, Catherine Chapelon-Abric, Céline Delestrain, Julien Haroche, Ralph Epaud, Ulrich Meinzer, Simon Chauveau, Fleur Cohen-Aubart, Mickaël Catinon, Florence Jeny, Odile Macchi, Sylvain Le Jeune, Hilario Nunes, Michel Vincent, Paul-André Rosental, Manon Brocvielle, Marie-Hélène Odièvre, Marie-Emeline Montagne, S. Mattioni, Dominique Valeyre, Karine Juvin, Annick Clement, Dominique Israël-Biet, A. Dossier, Nadia Nathan, Jacques Brouard, François Lionnet, Lucile Sesé, Rola Abou Taam, Christophe Delacourt, Marie Mittaine, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Pneumologie et allergologie pédiatriques [CHU Jeanne de Flandre, Lille], Hôpital Jeanne de Flandre [Lille], Université de Lille, Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de Pneumologie, soins intensifs (Pneumo - HEGP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], CHU Tenon [AP-HP], Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPC), Centre d'histoire de Sciences Po (Sciences Po) (CHSP), Sciences Po (Sciences Po), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Observatoire du Samu Social de Paris, CHU Necker - Enfants Malades [AP-HP], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre des maladies respiratoires rares Respirare [CHI Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de médecine interne [Avicenne], Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Groupe Hospitalier Paris Saint-Joseph (hpsj), Laboratoire interdisciplinaire d'évaluation des politiques publiques (Sciences Po) (LIEPP), Centre d'études de l'emploi et du travail (CEET), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère du Travail, de l'Emploi et de la Santé, contract grant sponsor: European Research Council (ERC) / SILICOSISproject / Principal investigator: Paul-André Rosental, Contract grant number: ERC2011-ADG_20110406ˆProject ID: 295817. Statistical analysis: RespiFIL funds, European Project: 295449,EC:FP7:ERC,ERC-2011-ADG_20110406,DARTCH(2012), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'études européennes et de politique comparée (CEE), Centre d'histoire de Sciences Po (CHSP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po)
Subjects: Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, paediatric interstitial lung disease, [SDV]Life Sciences [q-bio], [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Occupational Exposure, medicine, Humans, sarcoidosis, Occupational lung disease, Occupations, Child, Inorganic particles, 030304 developmental biology, 0303 health sciences, Median score, rare lung diseases, business.industry, Dust, Environmental exposure, Environmental Exposure, medicine.disease, 3. Good health, 030228 respiratory system, Metal dust, Talc, Sarcoidosis, business, occupational lung disease
Abstract: International audience; Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
Published: 2021

7. Parsing Fabry Disease Metabolic Plasticity Using Metabolomics

Author: Agnès Boullier, Olivier Lidove, Carine Pilon, Raphaël Aubert, Tony Pereira, Olivier Benveniste, Franklin Ducatez, Stéphane Marret, Soumeya Bekri, Abdellah Tebani, Wladimir Mauhin, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier Diaconesses Croix Saint-Simon, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Systems biology, Medicine (miscellaneous), inborn errors of metabolism, Disease, Computational biology, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Metabolomics, Biogenic amine, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lysosomal storage diseases, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Fabry disease, systems biology, Omics, medicine.disease, metabolomics, 3. Good health, Enzyme, machine learning, chemistry, Medicine, Sphingomyelin, 030217 neurology & neurosurgery
Abstract: International audience; Background: Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal α-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype–phenotype correlation. FD could involve kidney, heart or central nervous system impairment that significantly decreases life expectancy. The advent of omics technologies offers the possibility of a global, integrated and systemic approach well-suited for the exploration of this complex disease. Materials and Methods: Sixty-six plasmas of FD patients from the French Fabry cohort (FFABRY) and 60 control plasmas were analyzed using liquid chromatography and mass spectrometry-based targeted metabolomics (188 metabolites) along with the determination of LysoGb3 concentration and GalA enzymatic activity. Conventional univariate analyses as well as systems biology and machine learning methods were used. Results: The analysis allowed for the identification of discriminating metabolic profiles that unambiguously separate FD patients from control subjects. The analysis identified 86 metabolites that are differentially expressed, including 62 Glycerophospholipids, 8 Acylcarnitines, 6 Sphingomyelins, 5 Aminoacids and 5 Biogenic Amines. Thirteen consensus metabolites were identified through network-based analysis, including 1 biogenic amine, 2 lysophosphatidylcholines and 10 glycerophospholipids. A predictive model using these metabolites showed an AUC-ROC of 0.992 (CI: 0.965–1.000). Conclusion: These results highlight deep metabolic remodeling in FD and confirm the potential of omics-based approaches in lysosomal diseases to reveal clinical and biological associations to generate pathophysiological hypotheses.
Published: 2021

8. Effet d’un traitement par hydroxychloroquine prescrit comme traitement de fond de rhumatismes inflammatoires chroniques ou maladies auto-immunes systémiques sur les tests diagnostiques et l’évolution de l’infection à SARS CoV-2 : étude de 871 patients☆

Author: Sofremip, Jean Schmidt, Elodie Drumez, Mathilde Roumier, Nathalie Costedoat-Chalumeau, Isabelle Melki, Snfmi, Olivier Aumaître, Fai R, Yannick Dieudonné, Emmanuelle Dernis, Aurélia Lanteri, Christophe Richez, Soumaya El Mahou, Thomas Barnetche, Patrice Cacoub, Viviane Queyrel, Ludovic Trefond, Marc André, Raphaèle Seror, Eric Hachulla, Alexandre Belot, Mathilde Devaux, Thierry Thomas, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre de Référence des Maladies auto-immunes systémiques rares d’Ile-de-France, Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service d'Immunologie Clinique et de Médecine Interne [HUS], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre National de Référence des Maladies Auto-immunes et Systémiques Rares Est Sud Ouest (CNR RESO), Service de Rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de pédiatrie générale, Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], CHU Necker - Enfants Malades [AP-HP], Service de Rhumatologie [Hôpital Pasteur, Nice], Hôpital Pasteur [Nice] (CHU), Centre de compétence des maladies auto-immunes et systémiques rares, Service de Médecine interrne [Hôpital Foch, Suresnes], Hôpital Foch [Suresnes], Service de Médecine Interne [CHU Amiens-Picardie], CHU Amiens-Picardie, Réseau d'Epidémiologie Clinique International Francophone [Amiens] (RECIF Amiens), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie [Saint-Etienne], CHU Saint-Etienne-Hôpital de Bellevue, Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], FRE3632, Centre National de la Recherche Scientifique (CNRS), Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Hôpital Femme Mère Enfant, HCL] (RAISE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 030203 arthritis & rheumatology, Gynecology, 0303 health sciences, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Rhumatismes inflammatoires chroniques, COVID-19, 3. Good health, 03 medical and health sciences, DMARD, 0302 clinical medicine, Rheumatology, medicine, Maladies auto-immunes systémiques, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, Lettre À La Rédaction, Hydroxychloroquine
Abstract: Journal Pre-proof; International audience
Published: 2021

9. NK Cell Patterns in Idiopathic Inflammatory Myopathies with Pulmonary Affection

Author: Stylianos Tomaras, Yves Allenbach, Marc Pawlitzki, Christopher Nelke, Saskia Räuber, Liesa Regner, Anne Schänzer, Olivier Benveniste, Eugen Feist, Werner Stenzel, Corinna Preuße, Rebecca Hasseli, Tobias Ruck, Heinz Wiendl, Leoni Rolfes, Sven G. Meuth, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University Hospital Düsseldorf, Kerckhoff-Klinik, Helios Department of Rheumatology, Sophie-v.-Boetticher-Straße 1, 39245 Gommern, Germany, Justus-Liebig-Universität Gießen (JLU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), and HAL-SU, Gestionnaire
Subjects: Adult, Male, inflammatory myopathy, QH301-705.5, Cell, Article, Flow cytometry, Inflammatory myopathy, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Cytotoxic T cell, antibodies, Biology (General), Receptor, Aged, 030304 developmental biology, Aged, 80 and over, 030203 arthritis & rheumatology, interstitial lung disease, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, natural killer cells, biology, medicine.diagnostic_test, business.industry, General Medicine, Middle Aged, NKG2D, medicine.disease, Pathophysiology, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Immunology, biology.protein, Female, Antibody, Lung Diseases, Interstitial, business, myositis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Pulmonary affection (PA) is associated with a substantial increase in morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). However, the underlying immune mechanisms of PA remain enigmatic and prompt deeper immunological analyses. Importantly, the Janus-faced role of natural killer (NK) cells, capable of pro-inflammatory as well as regulatory effects, might be of interest for the pathophysiologic understanding of PA in IIM. Methods: To extend our understanding of immunological alterations in IIM patients with PA, we compared the signatures of NK cells in peripheral blood using multi-color flow cytometry in IIM patients with (n = 12, of which anti-synthetase syndrome = 8 and dermatomyositis = 4) or without PA (n = 12). Results: We did not observe any significant differences for B cells, CD4, and CD8 T cells, while total NK cell numbers in IIM patients with PA were reduced compared to non-PA patients. NK cell alterations were driven by a particular decrease of CD56dim NK cells, while CD56bright NK cells remained unchanged. Comparisons of the cell surface expression of a large panel of NK receptors revealed an increased mean fluorescence intensity of NKG2D+ on NK cells from patients with PA compared with non-PA patients, especially on the CD56dim subset. NKG2D+ and NKp46+ cell surface levels were associated with reduced vital capacity, serving as a surrogate marker for clinical severity of PA. Conclusion: Our data illustrate that PA in IIM is associated with alterations of the NK cell repertoire, suggesting a relevant contribution of NK cells in certain IIMs, which might pave the way for NK cell-targeted therapeutic approaches.
Published: 2021

10. Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients

Author: Manon Chauvin, Martin Larsen, Bibiana Quirant, Paul Quentric, Karim Dorgham, Luca Royer, Hélène Vallet, Amelie Guihot, Béhazine Combadière, Christophe Combadière, Jaume Barallat, Julien Mayaux, Charles-Edouard Luyt, Alexis Mathian, Zahir Amoura, Jacques Boddaert, Fernando Armestar, Guy Gorochov, Eva Martinez-Caceres, Delphine Sauce, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Service d'Immunologie [CHU Pitié-Salpétrière], Centre d'Immunologie et de Maladies Infectieuses (CIMI), CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre de Gériatrie [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL-SU, Gestionnaire, and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Exacerbation, [SDV]Life Sciences [q-bio], clinical outcome, Disease, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, chemistry.chemical_compound, Cellular and Infection Microbiology, 0302 clinical medicine, immune system diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Coronavirus, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Clinical outcome, Neopterin, Brief Research Report, QR1-502, 3. Good health, Death, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biomarker (medicine), biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Microbiology (medical), Critical Illness, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Population, Microbiology, 03 medical and health sciences, death, medicine, Humans, education, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, Innate immune system, business.industry, SARS-CoV-2, COVID-19, Biomarker, chemistry, neopterin, business, 030217 neurology & neurosurgery
Abstract: HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.
Published: 2021

11. Effect of music on pain during wound closure

Author: Duroux, Clément, Fainelli, Manon, Dirhoussi, Zidane, Le Joncour, Alexandre, Bonier, Colombine, Zak, Cathia, Cornet, Raphael, Raynal, Pierre‐Alexis, Yordanov, Youri, Thiebaud, Pierre‐Clément, Service des Urgences [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre international de musicothérapie (CIM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: integumentary system, humanities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Effect of music on pain and anxiety during wound closure in the emergency department Skin wounds account for about 5% of emergency department (ED) visits and may cause pain and anxiety, related to the trauma and/or the therapeutic procedure. 1 Wound closure by stitches, the most commonly used technique, is potentially painful. French guidelines on pain management in the ED suggest using music as a non-pharmacologic analgesic procedure. In a meta-analysis on the analgesic efficacy of music, authors reported a significant reduction in postoperative pain and morphine consumption. 2 Few studies on music therapy have been
Published: 2021

12. Iron deficiency in patients with cancer: a prospective cross-sectional study

Author: Luporsi, Elisabeth, Turpin, Anthony, Massard, Vincent, Morin, Sophie, Chauffert, Bruno, Carnot, Aurélien, Cacoub, Patrice, Choukroun, Gabriel, Service d'oncologie médicale [ICL Alexis Vautrin], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Mécanismes de tumorigenèse et thérapies ciblées, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), UNICANCER, Institut Bergonié [Bordeaux], HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CARENFER Study Group, Université de Lille-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Gestionnaire, HAL Sorbonne Université 5, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cross-sectional study, medicine.medical_treatment, Medicine (miscellaneous), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, In patient, chemistry.chemical_classification, Chemotherapy, High prevalence, biology, Oncology (nursing), business.industry, Cancer, General Medicine, Iron deficiency, medicine.disease, 3. Good health, Ferritin, Medical–Surgical Nursing, 030104 developmental biology, chemistry, Transferrin, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: BackgroundDespite the deleterious consequences of iron deficiency (ID) in patients with cancer, underdiagnosis is frequent. The CARENFER study aimed to assess the prevalence of ID using both serum ferritin concentration and transferrin coefficient saturation (iron-saturation of transferrin, TSAT) index, as well as ID anaemia in patients with cancer.MethodsThis prospective cross-sectional study was conducted in 15 oncology units in France in 2019. All patients present in the medical unit during the 2-week study period, regardless of the type of tumour (solid or haematological) and treatment, were eligible. Serum ferritin concentration, TSAT index and haemoglobin level were determined. ID and ID-associated anaemia were defined according to European Society of Medical Oncology 2018 Guidelines: ID was defined either as ferritin ResultsA total of 1221 patients with different types of solid malignant tumours were analysed: median age 64 years; 89.4% under treatment for their cancer, mainly by chemotherapy (75.4%). Overall, ID was found in 57.9% (55.1–60.6) of patients. Among them, functional ID accounted for 64% of cases. ID anaemia was reported in 21.8% (19.6–24.2) of all patients with cancer. ID was highly prevalent in untreated (75/130, 57.4%) and non-anaemic (419/775, 54.1%) patients.ConclusionThis study highlights the high prevalence of ID in patients with cancer, whether or not associated with anaemia or treatment. These results emphasise the need to a better detection and management of ID in cancer, thereby optimising overall patient care.Trial registration numberClinicalTrials.gov Identifier: NCT03924271.
Published: 2021

13. Immune Thrombocytopenia Revealing Enriched IgG-4 Peri-Renal Rosai-Dorfman Disease Successfully Treated with Rituximab: A Case Report and Literature Review

Author: Sylvain Audia, Sébastien Humbert, Jean Fontan, Fleur Cohen-Aubart, Jean-François Emile, Philippe Maksud, Jerome Razanamahery, Julien Haroche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Medicine (General), [SDV]Life Sciences [q-bio], Case Report, 03 medical and health sciences, 0302 clinical medicine, R5-920, rituximab, immune system diseases, hemic and lymphatic diseases, Biopsy, medicine, Platelet, Rosai–Dorfman disease, Histiocyte, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Pathophysiology, 3. Good health, Histiocytosis, Rosai Dorfman disease, immune thrombocytopenia, 030220 oncology & carcinogenesis, Erdheim Chester disease, Immunology, Erdheim–Chester disease, Medicine, Rituximab, business, histiocytosis, 030215 immunology, medicine.drug
Abstract: Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (MAP2K1mutation, although peri-renal infiltration is highly suggestive of Erdheim-Chester disease. This overlapping association was described in men with mutation inMAP2K1gene. Macrophages are implicated in the pathophysiology of ITP in multiple ways, notably by the phagocytosis of opsonized platelets and their function of antigen-presenting cells able to stimulate autoreactive T cells. Histiocytic cells derivate from monocyte-macrophage lineage. Activation of macrophages in active histiocytosis is responsible for consequential platelet destruction in ITP associated histiocytosis. Finally, this case highlights a rare presentation of ITP revealing histiocytosis, both being efficiently treated with rituximab.
Published: 2021

14. Neutrophil–Platelet and Monocyte–Platelet Aggregates in COVID-19 Patients

Author: David Saadoun, Matheus Vieira, Michelle Rosenzwajg, Arsène Mekinian, David Klatzmann, Lucie Biard, Yacine Boulaftali, Aude Carillion, Patrice Cacoub, Olivier Paccoud, Alexandre Le Joncour, Joe-Elie Salem, Georgina Maalouf, Anne-Geneviève Marcelin, Helene Bugaut, Jean-Christophe Corvol, Mathieu Vautier, Gestionnaire, HAL Sorbonne Université 5, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Platelets, 2019-20 coronavirus outbreak, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Figure 1, Neutrophils, References 25, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Monocytes, 03 medical and health sciences, 0302 clinical medicine, interleukin 6 receptor WORD COUNT :1197, Medicine, Platelet, thrombosis, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, business.industry, Monocyte, COVID-19 SARS-CoV-2 Platelets Neutrophils Monocytes Leukocytes-Platelets aggregates thrombosis interleukin 6 receptor WORD COUNT :1197 References 25, COVID-19, Hematology, Leukocytes-Platelets aggregates, Table 1, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world. Besides severe pneumonia with acute respiratory distress syndrome (ARDS), it has been more recently highlighted that SARS-CoV-2 could predispose to thrombotic disease, both in venous and arterial circulations.[1] Lung autopsy from severe COVID-19 patients revealed high recruitment of innate immune cells including neutrophils and macrophages contributing to the cytokine storm as well as microthrombi.[2] Given the central role of platelets in inflammation and thrombosis, and more specifically leucocyte–platelet aggregates that have been implicated in arterial and venous thrombosis, we aimed to explore neutrophil–platelet aggregate (NPA) and monocyte–platelet aggregate (MPA) in patients hospitalized in a medical ward for COVID-19 infection.
Published: 2020

15. The role of interferons type I, II and III in myositis: A review

Author: Loïs Bolko, Nozomu Tawara, Océane Landon-Cardinal, Olivier Benveniste, Yves Allenbach, Céline Anquetil, Wei Jiang, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, Gestionnaire, Hal Sorbonne Université, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, dermatomyositis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], anti-synthetase syndrome, Gene Expression, sporadic inclusion body myositis, Context (language use), Antisynthetase syndrome, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Interferon, medicine, Humans, Myopathy, Muscle, Skeletal, Myositis, Mini‐symposium, business.industry, General Neuroscience, Gene Expression Profiling, Interstitial lung disease, interferon, Dermatomyositis, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Cytokine, Immunology, Interferon Type I, Neurology (clinical), medicine.symptom, business, anti‐synthetase syndrome, myositis, 030217 neurology & neurosurgery, medicine.drug
Abstract: The classification of idiopathic inflammatory myopathies (IIM) is based on clinical, serological and histological criteria. The identification of myositis‐specific antibodies has helped to define more homogeneous groups of myositis into four dominant subsets: dermatomyositis (DM), antisynthetase syndrome (ASyS), sporadic inclusion body myositis (sIBM) and immune‐mediated necrotising myopathy (IMNM). sIBM and IMNM patients present predominantly with muscle involvement, whereas DM and ASyS patients present additionally with other extramuscular features, such as skin, lung and joints manifestations. Moreover, the pathophysiological mechanisms are distinct between each myositis subsets. Recently, interferon (IFN) pathways have been identified as key players implicated in the pathophysiology of myositis. In DM, the key role of IFN, especially type I IFN, has been supported by the identification of an IFN signature in muscle, blood and skin of DM patients. In addition, DM‐specific antibodies are targeting antigens involved in the IFN signalling pathways. The pathogenicity of type I IFN has been demonstrated by the identification of mutations in the IFN pathways leading to genetic diseases, the monogenic interferonopathies. This constitutive activation of IFN signalling pathways induces systemic manifestations such as interstitial lung disease, myositis and skin rashes. Since DM patients share similar features in the context of an acquired activation of the IFN signalling pathways, we may extend underlying concepts of monogenic diseases to acquired interferonopathy such as DM. Conversely, in ASyS, available data suggest a role of type II IFN in blood, muscle and lung. Indeed, transcriptomic analyses highlighted a type II IFN gene expression in ASyS muscle tissue. In sIBM, type II IFN appears to be an important cytokine involved in muscle inflammation mechanisms and potentially linked to myodegenerative features. For IMNM, currently published data are scarce, suggesting a minor implication of type II IFN. This review highlights the involvement of different IFN subtypes and their specific molecular mechanisms in each myositis subset., Pathological role of interferon in dermatomyositis.
Published: 2021

16. NanoString technology distinguishes anti‐TIF‐1γ+ from anti‐Mi‐2+ dermatomyositis patients

Author: Randi Koll, Pascale Eede, Anne Schänzer, Kiara Freitag, Hans-Hilmar Goebel, C. Preusse, Lucie Heinzeling, Udo Schneider, Werner Stenzel, Waltraud Froehlich, Josefine Radke, Olivier Benveniste, Yves Allenbach, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ludwig-Maximilians-Universität München (LMU), Universitätsklinikum Erlangen [Erlangen], Freie Universität Berlin, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Justus-Liebig-Universität Gießen (JLU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Oncology, Male, dermatomyositis, Disease, immunology [Signaling Lymphocytic Activation Molecule Family], 0302 clinical medicine, Neoplasms, immunology [Transcription Factors], NanoString, complications [Dermatomyositis], metabolism [Transcription Factors], TIF‐1γ, Mini‐symposium, General Neuroscience, Middle Aged, pathology [Neoplasms], Prognosis, 3. Good health, medicine.anatomical_structure, Phenotype, diagnosis [Dermatomyositis], Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], myositis‐specific antibody, Adult, medicine.medical_specialty, Proximal muscle weakness, Malignancy, immunology [Neoplasms], Pathology and Forensic Medicine, 03 medical and health sciences, Therapeutic approach, Signaling Lymphocytic Activation Molecule Family, TIF-1γ, Internal medicine, medicine, immunology [Autoantibodies], Humans, ddc:610, skeletal muscle, Mi-2, Mi‐2, Autoantibodies, immunology [Dermatomyositis], myositis-specific antibody, business.industry, immunology [Gene Expression Regulation], Autoantibody, Skeletal muscle, Cancer, Dermatomyositis, medicine.disease, 030104 developmental biology, Gene Expression Regulation, Neurology (clinical), business, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Dermatomyositis (DM) is a systemic idiopathic inflammatory disease affecting skeletal muscle and skin, clinically characterized by symmetrical proximal muscle weakness and typical skin lesions. Recently, myositis‐specific autoantibodies (MSA) became of utmost importance because they strongly correlate with distinct clinical manifestations and prognosis. Antibodies against transcription intermediary factor 1γ (TIF‐1γ) are frequently associated with increased risk of malignancy, a specific cutaneous phenotype and limited response to therapy in adult DM patients. Anti‐Mi‐2 autoantibodies, in contrast, are typically associated with classic DM rashes, prominent skeletal muscle weakness, better therapeutic response and prognosis, and less frequently with cancer. Nevertheless, the sensitivity of autoantibody testing is only moderate, and alternative reliable methods for DM patient stratification and prediction of cancer risk are needed. To further investigate these clinically distinct DM subgroups, we herein analyzed 30 DM patients (n = 15 Mi‐2+ and n = 15 TIF‐1 γ+) and n = 8 non‐disease controls (NDC). We demonstrate that the NanoString technology can be used as a very sensitive method to clearly differentiate these two clinically distinct DM subgroups. Using the nCounter PanCancer Immune Profiling Panel™, we identified a set of significantly dysregulated genes in anti‐TIF‐1γ+ patient muscle biopsies including VEGFA, DDX58, IFNB1, CCL5, IL12RB2, and CD84. Investigation of type I IFN‐regulated transcripts revealed a striking type I interferon signature in anti‐Mi‐2+ patient biopsies. Our results help to stratify both subgroups and predict, which DM patients require an intensified diagnostic procedure and might have a poorer outcome. Potentially, this could also have implications for the therapeutic approach., Dermatomyositis (DM) is a systemic idiopathic inflammatory disease affecting skeletal muscle and skin, clinically characterized by symmetrical proximal muscle weakness and typical skin lesions. Genetic profiling of anti‐TIF‐1γ+ and ‐Mi‐2+ dermatomyositis patients’ skeletal muscle biopsies revealed subgroup‐specific signatures, which helps to stratify both subgroups and predict, which DM patients require an intensified diagnostic procedure and might have a poorer outcome.
Published: 2021

17. MRI and muscle imaging for idiopathic inflammatory myopathies

Author: Damien Bachasson, Céline Anquetil, Olivier Benveniste, Samuel Malartre, Yves Allenbach, Guillaume Mercy, Elissone Sarkis, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre de Recherche en Myologie, Gestionnaire, Hal Sorbonne Université, and Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière]
Subjects: 0301 basic medicine, medicine.medical_specialty, idiopathic inflammatory myopathies, Biopsy, [SDV]Life Sciences [q-bio], ultra sound imaging, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Muscle, Skeletal, Myositis, Ultrasonography, Shear wave elastography, Mini‐symposium, Muscle biopsy, medicine.diagnostic_test, business.industry, General Neuroscience, Ultrasound, Brain, Magnetic resonance imaging, Gold standard (test), medicine.disease, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Idiopathic inflammatory myopathies, Positron emission tomography, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery, MRI
Abstract: Although idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases nearly all patients display muscle inflammation. Originally, muscle biopsy was considered as the gold standard for IIM diagnosis. The development of muscle imaging led to revisiting not only the IIM diagnosis strategy but also the patients’ follow‐up. Different techniques have been tested or are in development for IIM including positron emission tomography, ultrasound imaging, ultrasound shear wave elastography, though magnetic resonance imaging (MRI) remains the most widely used technique in routine. Whereas guidelines on muscle imaging in myositis are lacking here we reviewed the relevance of muscle imaging for both diagnosis and myositis patients’ follow‐up. We propose recommendations about when and how to perform MRI on myositis patients, and we describe new techniques that are under development., Muscle imaging and especially muscle MRI is a powerful technique for both IIM diagnosis and follow‐up. Muscle MRI is actually the best muscle imaging technique in routine, and it is widely used, but guidelines determining when and how to use it in myositis patients are lacking.
Published: 2021

18. Development and clinical validation of a simple and fast UPLC-ESI-MS/MS method for simultaneous quantification of nine kinase inhibitors and two antiandrogen drugs in human plasma: interest for their therapeutic drug monitoring

Author: Fleur Cohen Aubart, Baptiste Abbar, Noël Zahr, Bruno Pinna, Nadine Tissot, Joe-Elie Salem, Christian Funck-Brentano, Damien roos Weil, Benoit Llopis, Paul Gougis, Madalina Uzunov, Luca Campedel, Pascal Robidou, Joseph Gligorov, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut E3M [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: antiandrogens, therapeutic drug monitoring, Clinical Biochemistry, Pharmaceutical Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Palbociclib, 01 natural sciences, Analytical Chemistry, oral targeted therapies, chemistry.chemical_compound, Pharmacokinetics, Tandem Mass Spectrometry, Drug Discovery, medicine, Humans, liquid chromatography, kinase inhibitors, Protein Kinase Inhibitors, Chromatography, High Pressure Liquid, Spectroscopy, Active metabolite, mass spectrometry, Cobimetinib, Chromatography, medicine.diagnostic_test, 010405 organic chemistry, Chemistry, 010401 analytical chemistry, Reproducibility of Results, Androgen Antagonists, 0104 chemical sciences, Dasatinib, Pharmaceutical Preparations, Nilotinib, Therapeutic drug monitoring, Pharmacodynamics, Drug Monitoring, Chromatography, Liquid, medicine.drug
Abstract: International audience; Kinase inhibitors (KIs) and antiandrogen drugs (AAs) are oral anticancer drugs with narrow therapeutic index that exhibit high inter-and intra-individual variability. We describe here a UPLC-MS/MS method for the simultaneous quantification of nine KIs: cobimetinib, dasatinib, ibrutinib, imatinib, nilotinib, palbociclib, ruxolitinib, sorafenib and vemurafenib; two active metabolites of them: N-desmethyl imatinib, N-oxide sorafenib; and two AAs: abiraterone and enzalutamide; with short pre-treatment and run time in order to be easily used in clinical practice for their therapeutic drug monitoring (TDM) and facilitating pharmacokinetics and pharmacokinetics/pharmacodynamics studies. Plasma samples were prepared by a single-step protein precipitation. Analytes were separated on a Waters Acquity UPLC ® T3 HSS C18 column by non-linear gradient elution; with subsequent detection by Xevo ® TQD triple quadrupole tandem mass spectrometer in a positive ionization mode. Analysis time was 2.8 minutes per run, and all analytes eluted within 1.46-1.97 minutes. The analytical performance of the method in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, dilution integrity and stability of analytes under different conditions met all criteria for a bioanalytical method for the quantification of drugs. The calibration curves were linear over the range of 1-500 ng/mL for abiraterone, dasatinib and ibrutinib; 5-500 ng/mL for cobimetinib and palbociclib; 10-5,000 ng/mL for imatinib, N-desmethyl imatinib, nilotinib, sorafenib, N-oxide sorafenib and ruxolitinib; 100-50,000 ng/mL for enzalutamide and 100-100,000 ng/mL for vemurafenib with coefficient of correlation above 0.995 for all analytes. This novel method was successfully applied to TDM in clinical practice.
Published: 2021

19. Specific microbiome profile in Takayasu’s arteritis and giant cell arteritis

Author: Desbois, Anne claire, Desbois, Anne, Ciocan, Dragos, Saadoun, David, Perlemuter, Gabriel, Cacoub, Patrice, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Male, 0301 basic medicine, Cell biology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Giant Cell Arteritis, Takayasu's arteritis, Pathogenesis, 030204 cardiovascular system & hematology, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Sepsis, Internal medicine, Large vessel vasculitis, Humans, Medicine, In patient, Microbiome, Arteritis, Cytophagia, Aged, Aged, 80 and over, Multidisciplinary, business.industry, Microbiota, Computational Biology, Middle Aged, medicine.disease, Takayasu Arteritis, 3. Good health, Giant cell arteritis, 030104 developmental biology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Metagenome, Female, Disease Susceptibility, Metagenomics, business, Biomarkers, Bacterial dna
Abstract: Recent studies have provided evidence of a close link between specific microbiota and inflammatory disorders. While the vessel wall microbiota has been recently described in large vessel vasculitis (LVV) and controls, the blood microbiome in these diseases has not been previously reported (LVV). We aimed to analyse the blood microbiome profile of LVV patients (Takayasu’s arteritis [TAK], giant cell arteritis [GCA]) and healthy blood donors (HD). We studied the blood samples of 13 patients with TAK (20 samples), 9 patients with GCA (11 samples) and 15 HD patients. We assessed the blood microbiome profile by sequencing the 16S rDNA blood bacterial DNA. We used linear discriminant analysis (LDA) coupled with linear discriminant effect size measurement (LEfSe) to investigate the differences in the blood microbiome profile between TAK and GCA patients. An increase in the levels of Clostridia, Cytophagia and Deltaproteobacteria and a decrease in Bacilli at the class level were found in TAK patients compared with HD patients (LDA > 2, p 2; p
Published: 2021

20. Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic)

Author: Jean Sibilia, François Rieger, Christelle Volteau, Jean-François Viallard, Mikael Ebbo, Joel Poupon, Mohamed Hamidou, Jean-Benoit Hardouin, Antoine Néel, Benjamin Gaborit, Eric Hachulla, Zahir Amoura, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Université de Strasbourg (UNISTRA), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Université de Lille, Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Gestionnaire, Hal Sorbonne Université, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, medicine.drug_class, Autoimmune diseases, [SDV]Life Sciences [q-bio], Neutropenia, Antibodies, Monoclonal, Humanized, Severity of Illness Index, 03 medical and health sciences, chemistry.chemical_compound, Systemic lupus erythematosus, 0302 clinical medicine, Arsenic trioxide, Internal medicine, Clinical endpoint, Humans, Lupus Erythematosus, Systemic, Medicine, Adverse effect, 030203 arthritis & rheumatology, business.industry, medicine.disease, Phase II clinical trial, Rheumatology, 3. Good health, [SDV] Life Sciences [q-bio], Treatment, Treatment Outcome, 030104 developmental biology, chemistry, Corticosteroid, lcsh:RC925-935, Osteitis, business, Immunosuppressive Agents, Research Article
Abstract: Background Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE. Methods This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS). Results Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P Conclusions A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy. Trial registration ClinicalTrials.gov, NCT01738360 registered 30 November 2012
Published: 2021

21. Efficacy and safety of steroid-sparing treatments in giant cell arteritis according to the glucocorticoids tapering regimen: A systematic review and meta-analysis

Author: Agnès Dechartres, David Saadoun, Florence Tubach, Patrice Cacoub, Anne-Laure Gerard, Youri Yordanov, Noémie Simon-Tillaux, Gestionnaire, Hal Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Urgences Adultes [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Urgences [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Giant Cell Arteritis, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Randomized controlled trial, law, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Prospective cohort study, Adverse effect, Glucocorticoids, business.industry, Hydroxychloroquine, 3. Good health, [SDV] Life Sciences [q-bio], Meta-analysis, Regimen, Methotrexate, chemistry, Systematic review, Drug Therapy, Combination, Steroids, Steroid-sparing treatment, business, Adjuvant, medicine.drug
Abstract: Objectives To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome) and to assess the impact of GC tapering regimen on adjuvant effectiveness. Methods For this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, trial registries, from inception to November 2020. We included all randomized controlled trials (RCTs) and controlled prospective studies evaluating adjuvant treatments in GCA, without date or language restriction. Two reviewers independently selected studies, extracted data and assessed risk of bias. Quality of evidence was summarised with GRADE. Results Of the 680 records identified, 16 studies were included (1,068 participants) evaluating various adjuvant therapies compared to GC only. No study compared adjuvants with each other. Risk of bias was high in 5/7 trials evaluating our primary outcome. Risk of relapse at week 52 was reduced for only the anti-IL6 and IL6-receptor drug class versus the control (RR=0.45, 95%CI 0.30–0.66, I2=38%), particularly tocilizumab (RR=0.38, 95%CI 0.23–0.63, I2=42%) with a moderate quality of evidence. We found no significant interaction according to GC tapering regimen. Our meta-analysis did not show a significant benefit for methotrexate. Except for dapsone, ciclosporine and hydroxychloroquine, other adjuvants did not seem to show increased risk of adverse events. Conclusions Tocilizumab seems to reduce the relapse rate in GCA at week 52 but the quality of evidence was moderate. No other molecule has shown efficacy. No significant interaction on relapse rate by GC tapering regimen was found. Study registration PROSPERO CRD42020172011.
Published: 2021

22. Apremilast in Refractory Behçet’s Syndrome: A Multicenter Observational Study

Author: Matheus Vieira, Solène Buffier, Mathieu Vautier, Alexandre Le Joncour, Yvan Jamilloux, Mathieu Gerfaud-Valentin, Laurence Bouillet, Estibaliz Lazaro, Stéphane Barete, Laurent Misery, Delphine Gobert, Tiphaine Goulenok, Olivier Fain, Karim Sacre, Pascal Sève, Patrice Cacoub, Cloé Comarmond, David Saadoun, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hopital de Bohars - CHRU Brest (CHU - BREST ), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), HAL-SU, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, efficacy, apremilast, Arthritis, Gastroenterology, Cohort Studies, 030207 dermatology & venereal diseases, 0302 clinical medicine, joint, Immunology and Allergy, Original Research, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Behçet, Behcet Syndrome, Anti-Inflammatory Agents, Non-Steroidal, cohort, Middle Aged, Thalidomide, 3. Good health, Drug Combinations, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Cohort, Female, France, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.drug, lcsh:Immunologic diseases. Allergy, Adult, musculoskeletal diseases, safety, skin, medicine.medical_specialty, Immunology, Mucocutaneous zone, 03 medical and health sciences, Refractory, Internal medicine, medicine, Humans, Sex organ, 030203 arthritis & rheumatology, business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Discontinuation, Clinical trial, Prednisone, Apremilast, lcsh:RC581-607, Colchicine, business
Abstract: ObjectiveMucocutaneous and joint disorders are the most common manifestations in Behçet’s syndrome (BS) and are frequently clustered in the so-called minor forms of BS. There remains a need for safe and effective treatment for joint lesions in BS. We report the long-term safety and effectiveness of apremilast in refractory joint and mucocutaneous manifestations of BS.MethodsFrench nationwide multicenter study including 50 BS patients with either active joint and/or mucocutaneous manifestations resistant to colchicine and/or DMARDs. Patients received apremilast 30 mg twice a day. Primary effectiveness endpoint was the proportion of patients with complete response (CR) of articular symptoms at month 6 (M6), defined as resolution of inflammatory arthralgia and arthritis, with joint count equal to zero.ResultsAt inclusion, the median tender and swollen joint count was of 4 [2-6] and 2 [1-2], respectively. The proportion of CR in joint disease at M6 was 65% (n = 15/23), and 17% (n = 4/23) were partial responders. CR of oral and genital ulcers, and pseudofolliculitis at M6 was 73% (n = 24/33), 94% (n = 16/17) and 71% (n = 10/14), respectively. The overall response at M6 was 74% for the entire cohort and 70% for the mucocutaneous-articular cluster (n = 27). The median Behçet’s syndrome activity score significantly decreased during study period [50 (40–60) vs. 20 (0–40); p <0.0001]. After a median follow-up of 11 [6-13] months, 27 (54%) patients were still on apremilast. Reasons for apremilast withdrawal included adverse events (n = 15, 30%) and treatment failure (n = 8, 16%). Thirty-three (66%) patients experienced adverse events, mostly diarrhea (n = 19, 38%), nausea (n = 17, 34%) and headache (n = 16, 32%).ConclusionApremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.
Published: 2021

23. Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: A pilot study

Author: Mathieu Vautier, Arsène Mekinian, Amine Ghembaza, Gaëlle Leroux, Sébastien Rivière, Patrice Cacoub, David Saadoun, Fanny Domont, Jonathan Boutemy, Hélène Maillard, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Vasculitis, medicine.medical_specialty, Time Factors, Biologic, Hepatitis C virus, [SDV]Life Sciences [q-bio], Immunology, Pilot Projects, medicine.disease_cause, Antibodies, Monoclonal, Humanized, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, hemic and lymphatic diseases, Immunology and Allergy, Medicine, Humans, Immunologic Factors, Aged, 030203 arthritis & rheumatology, business.industry, Remission Induction, medicine.disease, Belimumab, Cryoglobulinemia, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Peripheral neuropathy, Treatment Outcome, Rituximab, Drug Therapy, Combination, Female, Osteitis, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; Objective: To report the efficacy of rituximab plus belimumab in patients with refractory cryoglobulinemia vasculitis (CV).Methods: Belimumab was administered intravenously at a dose of 10 mg/kg on days 0, 14, 28 and then every month in association with rituximab in 4 patients with refractory CV. Demographic, clinical and laboratory characteristics, treatment modalities and outcomes were recorded.Results: All patients had type II IgM Kappa cryoglobulinemia, which was associated with primary Sjögren syndrome (n = 1), hepatitis C virus infection (n = 1), and essential (n = 2). Main manifestations of CV included purpura (n = 4), arthralgia and peripheral neuropathy (n = 3), and glomerulonephritis and skin ulcers (n = 1). In all cases, CV was refractory and/or relapse following rituximab. Intravenous belimumab infusion along with rituximab resulted in rapid clinical response in the four patients. Osteitis and recurrent urinary tract infections occurred in two patients.Conclusion: Belimumab along with rituximab showed promising results in refractory patients with CV.
Published: 2021

24. Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

Author: Valérie Thiers, Aurélie Poli, Vincent Caval, François Hafezi, Morgane Lemaire, Hélène Laude, Hervé Blanc, Jean-Pierre Vartanian, Marco Vignuzzi, Danielle Perez-Bercoff, Simon Wain-Hobson, Alexis Mathian, Rodolphe Suspène, Zahir Amoura, Oliver Hunewald, Gestionnaire, Hal Sorbonne Université, Luxembourg Institute of Health (LIH), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], This work was supported by Fonds National de la Recherche du Luxembourg (INTER/Mobility/16/1154722/APO-SLE), by Ministère de l’Education et de la Recherche du Luxembourg and by Institut Pasteur Paris. FH was supported by FNR-PRIDE scheme (PRIDE/11012546/NEXTIMMUNE)., Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Programmed cell death, Science, [SDV]Life Sciences [q-bio], Cell, Immunology, Peripheral blood mononuclear cell, Polymorphism, Single Nucleotide, Gene Expression Regulation, Enzymologic, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Polymorphism (computer science), Genetics, Medicine, Humans, Lupus Erythematosus, Systemic, Telomerase reverse transcriptase, APOBEC Deaminases, Telomerase, Germ-Line Mutation, 030304 developmental biology, Cancer, 0303 health sciences, Multidisciplinary, Cell Death, business.industry, Interferon-alpha, Hydroxychloroquine, medicine.disease, 3. Good health, Up-Regulation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: APOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.
Published: 2021

25. Alcohol consumption among French physicians: A cross-sectional study

Author: Pierre-Clément Thiebaud, Diane Naouri, Youri Yordanov, Jennifer Truchot, Camille Martin, Alexandre Le Joncour, Service des Urgences [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Gestionnaire, Hal Sorbonne Université, Service d'Urgences Adultes [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Alcohol Drinking, Cross-sectional study, [SDV]Life Sciences [q-bio], Population, Computer-assisted web interviewing, Audit, Toxicology, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Physicians, Prevalence, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, education, Pharmacology, Consumption (economics), education.field_of_study, Alcohol Use Disorders Identification Test, Alcohol-related disorders, Occupational health, Illicit Drugs, business.industry, Doctors, Middle Aged, Mental health, 3. Good health, [SDV] Life Sciences [q-bio], Alcoholism, Psychiatry and Mental health, Cross-Sectional Studies, AUDIT score, Family medicine, Female, France, business, Alcohol, 030217 neurology & neurosurgery
Abstract: International audience; Background: Data regarding French physicians' alcohol behaviours are scarce and most studies address this issue within the population of either medical students or residents. We aim to describe and assess the prevalence of hazardous alcohol consumption among French physicians.Methods: A regional, cross-sectional, survey was conducted in 2018 using an online questionnaire among Parisian general practitioners and hospital doctors. Hazardous alcohol consumption was defined by an Alcohol Use Disorders Identification Test (AUDIT) score ≥ 8. Data were analysed in 2020.Results: Five hundred fifteen physicians completed the survey: 108 general practitioners and 407 hospital physicians. The median age was 40 years [32-55] and 59 % were women. They considered their physical and mental health as average or bad in 10 % and 8% of cases, respectively. The prevalence of hazardous alcohol consumption was 12.6 %. Among the 65 physicians with hazardous alcohol consumption, 27 (41.5 %) did not considered it as risky and four (6.2 %) mentioned a potentially negative impact on patients' care. Factors independently associated with hazardous alcohol consumption were illegal drugs consumption (OR 4.62 [2.05-10.37]) and fixed term contract for hospital doctors (OR 2.69 [1.14-6.36]).Conclusions: The prevalence of hazardous alcohol consumption among French physicians was 12.6 %. Illegal substance users and fix-termed contract hospital doctors were more likely to have risky alcohol consumption. A large-scale national study would confirm the factors associated with hazardous alcohol consumption and could explore the efficacy of preventive measures to insure the safety and health of physicians and their patients.
Published: 2021

26. [Pericarditis]

Author: Marques, Cindy, Cacoub, Patrice, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: MESH: Colchicine, MESH: Interleukin 1 Receptor Antagonist Protein, MESH: Humans, [SDV]Life Sciences [q-bio], Pericarditis, MESH: Aspirin, MESH: Pericarditis, MESH: Prospective Studies, MESH: Recurrence
Abstract: International audience; "Pericarditis Acute pericarditis is a common disease, most often idiopathic or viral. This is usually a mild condition but recurrences are frequent. The predominant pathophysiological hypothesis is that of underlying dysimmune disorders, involving an inflammatory response of the innate immune system typical of "autoinflammatory diseases", mainly mediated by interleukin-1 [IL-1] with activation of inflammasome; and an adaptive immune system response, typical of «autoimmune diseases», primarily mediated by autoantibodies and autoreactive T cells. The clinical picture associates fever, chest pain, changes in the electrocardiogram and possible pericardial effusion. Treatment is based on the combination of aspirin/nonsteroidal anti-inflammatory drugs and colchicine for several weeks. In refractory pericarditis, low dose corticosteroid therapy and / or immunosuppressive agents have been proposed with limited efficacy. Growing evidency suggest a place for IL-1 receptor antagonists in the treatment of recurrent pericarditis. Many studies have shown the effectiveness of anakinra with a good safety profile. Other IL-1 receptor antagonists have shown promising results (canakinumab, rilonacept). Further evaluation in larger prospective clinical trials is needed to confirm the long-term efficacy and safety of anti-IL1."
Published: 2021

27. Correspondance on ‘Clinical characteristics and genetic analyses of 187 patients with undefined autoinflammatory diseases’

Author: Patrice Cacoub, Guillaume Sarrabay, Gonçalo Boleto, Véronique Hentgen, L. Biard, Guilaine Boursier, Isabelle Touitou, Isabelle Koné-Paut, David Saadoun, Carolla El Chamieh, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Herrada, Anthony
Subjects: 0301 basic medicine, medicine.medical_specialty, cryopyrin-associated periodic syndromes, Immunology, Familial Mediterranean fever, Disease, Recurrent aphthous stomatitis, General Biochemistry, Genetics and Molecular Biology, Malaise, polymorphism, 03 medical and health sciences, Pericarditis, 0302 clinical medicine, Rheumatology, familial Mediterranean fever, Internal medicine, medicine, Immunology and Allergy, Stomatitis, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Cryopyrin-associated periodic syndrome, medicine.disease, Pharyngitis, 3. Good health, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, inflammation, medicine.symptom, genetic, business
Abstract: We read with great interest the article by Ter Haar et al 1 who describe the clinical characteristics, treatment response and genetic findings in a cohort of patients (n=187) with undefined systemic autoinflammatory diseases (sAIDs). The authors observed that patients with pericarditis were older at disease onset and had milder disease whereas patients with intellectual impairment were younger at disease onset and often had affected relatives. Of note, among patients with recurrent disease course, 30% (n=53/180) had aphthous stomatitis. Moreover, after complete gene screening, screening of most relevant exons or screening of most relevant point mutations, 9.4% (n=15/159) of patients carried likely pathogenic variants or variants of uncertain significance. Our recent French multicentre study on targeted next-generation sequencing (NGS) gives further insight into the clinical characteristics and genetic findings in patients with sAIDs associated with recurrent aphthous stomatitis (RAS). RAS (ie, adult onset, association with other features such as fever and malaise) can represent a diagnostic challenge. RAS especially when associated with fever, pharyngitis and lymphadenopathy may be the first presentation of sAIDs.2 sAIDs arise from impaired inflammatory responses due to variants in gene coding proteins …
Published: 2020

28. Iron deficiency markers in patients undergoing iron replacement therapy: a 9-year retrospective real-world evidence study using healthcare databases

Author: Gaël Nicolas, Patrice Cacoub, Katell Peoc'h, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, Chronic condition, medicine.medical_specialty, Databases, Factual, Iron, [SDV]Life Sciences [q-bio], lcsh:Medicine, Context (language use), 030204 cardiovascular system & hematology, computer.software_genre, Biochemistry, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Medical prescription, lcsh:Science, Aged, Retrospective Studies, Inflammation, Multidisciplinary, biology, Database, Transferrin saturation, business.industry, Public health, lcsh:R, Transferrin, Diagnostic markers, Iron Deficiencies, Iron deficiency, Middle Aged, medicine.disease, 3. Good health, Ferritin, Chronic Disease, Ferritins, Cohort, Hematinics, biology.protein, Female, lcsh:Q, France, business, computer, Biomarkers
Abstract: The diagnosis and treatment of iron deficiency is a primary public health goal. This study aimed to make an inventory of the use of biomarkers to assess the iron supply in patients given iron replacement therapy. A retrospective longitudinal real-world study of a cohort of patients receiving iron replacement therapy was conducted using data from healthcare coverage databases between January 2006 and December 2015 in France. The frequency of oral or intravenous iron treatment episodes preceded and/or followed by a biological assessment of iron deficiency was described. We then differentiate patients with or without chronic inflammatory diseases, which could impact the prescription. The evolution between 2006 and 2015 was also studied. The 96,724 patients received an average of 4.9 administrations of iron per patient, corresponding to 1.7 treatment episodes. In one-third of treatment episodes (34.6%), patients had a pre-treatment biological assessment, 15.5% a post-treatment assessment, and 7.3% both. The post-treatment measure of iron supply markers (i.e., Ferritin and transferrin saturation) was more frequent in patients suffering from chronic inflammatory diseases than in those without underlying chronic condition (22.6% to 41.0% vs. 3.1%; p
Published: 2020

29. Emerging Molecular Targets for the Treatment of Refractory Sarcoidosis

Author: Gonçalo Boleto, Matheus Vieira, Anne Claire Desbois, David Saadoun, Patrice Cacoub, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP]
Subjects: Cyclophosphamide, Mini Review, [SDV]Life Sciences [q-bio], Azathioprine, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, medicine, sarcoidosis, Interleukin 6, granuloma, 030203 arthritis & rheumatology, lcsh:R5-920, therapy, biology, JAK inhibitors, business.industry, interleukin-6, Interleukin, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], chemistry, Granuloma, Immunology, biology.protein, Medicine, Methotrexate, Sarcoidosis, business, lcsh:Medicine (General), interleukin-1, medicine.drug
Abstract: International audience; Sarcoidosis is a multisystem granulomatous disease of unknown origin that has variable clinical course and can affect nearly any organ. It has a chronic course in about 25% of patients. Corticosteroids (CS) are the cornerstone of therapy but their long-term use is associated with cumulative toxicity. Commonly used CS-sparing agents include methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil. Twenty to forty percentage of sarcoidosis patients are refractory to these therapies or develop severe adverse events. Therefore, additional and targeted CS-sparing agents are needed for chronic sarcoidosis. Macrophage activation, interferon response, and formation of the granuloma are mainly mediated by T helper-1 responses. Different pro-inflammatory cytokines such as interleukin (IL)-8, IL-12, IL-6, and tumor necrosis factor-alpha (TNF-α) have been shown to be highly expressed in sarcoidosis-affected tissues. As a result of increased production of these cytokines, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is constitutively active in sarcoidosis. Several studies of biological agents that target TNF-α have reported their efficacy and appear today as a second line option in refractory sarcoidosis. Some case series report a positive effect of tocilizumab an anti-IL-6 monoclonal antibody in this setting. More recently, JAK inhibition appears as a new promising strategy. This review highlights key advances on the management of chronic refractory sarcoidosis. Novel therapeutic strategies and treatment agents to manage the disease are described.
Published: 2020

30. Performance of serum apolipoprotein-A1 as a sentinel of Covid-19

Author: Sepideh Akhavan, Marika Rudler, Dominique Bonnefont-Rousselot, Julien Mayaux, Bruno Fautrel, Clemence Franc, Yves Allenbach, Mehdi Sakka, Chantal Housset, Olivier Lucidarme, Vincent Calvez, Thierry Poynard, Frédérique Gandjbakhch, Jean Marc Lacorte, Olivier Deckmyn, Mathieu Vautier, F. Drane, Patrice Cacoub, Yen Ngo, Dominique Thabut, J.M. Castille, David Saadoun, Valentina Peta, Olivier Benveniste, Vlad Ratziu, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), BioPredictive [Paris], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Service de virologie [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Viral Diseases, Epidemiology, [SDV]Life Sciences [q-bio], Biochemistry, Geographical locations, law.invention, Medical Conditions, 0302 clinical medicine, law, Medicine and Health Sciences, Virus Testing, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, medicine.diagnostic_test, Liver Diseases, Haptoglobin, Middle Aged, Intensive care unit, Hospitals, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Intensive Care Units, Infectious Diseases, 030220 oncology & carcinogenesis, Medicine, Female, 030211 gastroenterology & hepatology, Apolipoprotein A1, France, Coronavirus Infections, Research Article, Adult, medicine.medical_specialty, Science, Pneumonia, Viral, Population, Gastroenterology and Hepatology, Betacoronavirus, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, medicine, Humans, European Union, education, Pandemics, Aged, Retrospective Studies, 030304 developmental biology, Plasma Proteins, Haptoglobins, Apolipoprotein A-I, SARS-CoV-2, business.industry, Biology and Life Sciences, Proteins, COVID-19, Covid 19, Retrospective cohort study, medicine.disease, United States, Health Care, Pneumonia, Health Care Facilities, Medical Risk Factors, Relative risk, biology.protein, Observational study, People and places, business, Liver function tests, Biomarkers
Abstract: BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 30 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (183,112 sera) and in France (18,316 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 234,881 and 26,056 sera). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.ResultsThe mean serum apolipoprotein-A1 levels in these populations began decreasing in January 2020, compared to the same 30 weeks in 2019. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 30 weeks, in both France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0;P=0.04).ConclusionApolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population with no new blood sample, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test. NCT01927133, CER-2020-14.Key PointsQuestionDoes serum apolipoprotein-A1 decrease could be a very early biomarker of SARS-CoV-2 pandemic?FindingsDuring the 30 weeks of 2020 we observed in two large cohorts of patients at risk of liver fibrosis a highly significant decrease of serum apolipoprotein-A1, not observed in previous years. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases, including the recovery period.MeaningApolipoprotein-A1 could be used as a sentinel of the pandemic in existing routine surveillance of the general population.
Published: 2020

31. Biotherapies in Uveitis

Author: Mathilde Leclercq, Sara Touhami, David Saadoun, Fanny Domont, Bahram Bodaghi, Georgina Maalouf, A.C. Desbois, Patrice Cacoub, Hôpital Charles Nicolle [Rouen], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL-SU, Gestionnaire, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, lcsh:Medicine, Topical treatment, Disease, Review, 03 medical and health sciences, chemistry.chemical_compound, tocilizumab, 0302 clinical medicine, Tocilizumab, medicine, Adalimumab, Therapeutic strategy, 030203 arthritis & rheumatology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Blindness, business.industry, lcsh:R, non-infectious uveitis, General Medicine, medicine.disease, Dermatology, Infliximab, Janus Associated Kinase (JAK) inhibitors, 3. Good health, anti-TNF-α (anti-tumor necrosis factor alpha) agent, chemistry, biotherapy, 030221 ophthalmology & optometry, business, Uveitis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Non-infectious uveitis (NIU) represents one of the leading causes of blindness in developed countries. The therapeutic strategy aims to rapidly control intra-ocular inflammation, prevent irremediable ocular damage, allow corticosteroid sparing and save the vision, and has evolved over the last few years. Anterior NIU is mostly managed with topical treatment in adults. However, for intermediate, posterior and pan-uveitis, notably when both eyes are involved, systemic treatment is usually warranted. Biotherapies are recommended in case of inefficacy or non-tolerance of conventional immunosuppressive drugs in non-anterior NIU. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are by far the most widely used, especially adalimumab (ADA) and infliximab (IFX). In case of sight-threatening uveitis in Behçet's disease or in case of risk of severe recurrences, respectively IFX and ADA may be recommended as first-line therapy. Many questions are left unanswered; how long to treat NIU, how to discontinue anti-TNF-α agents, what biologic to use in case of anti-TNF-α failure? The objective of this review is to present an updated overview of knowledge on the use of biological treatments in NIU.
Published: 2020

32. Foetal exposure to heavy metals and risk of atopic diseases in early childhood

Author: Lucile Sesé, Giuliana Ferrante, Lucia Calciano, Guy Huel, Raphael Lhote, Boris Dessimond, Ramen Munir Baloch, Isabella Annesi-Maesano, Giancarlo Pesce, Munawar Hussain Soomro, Cara Nichole Maesano, Martine Guinot, Benoit Travert, Julie Prud'homme, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli studi di Verona = University of Verona (UNIVR), Università degli studi di Palermo - University of Palermo, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Pesce G, Sesé L, Calciano L, Travert B, Dessimond B, Maesano CN, Ferrante G, Huel G, Prud'homme J, Guinot M, Soomro MH, Baloch RM, Lhote R, Annesi-Maesano I, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Verona (UNIVR), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, atopic dermatiti, Allergy, cadmium, [SDV]Life Sciences [q-bio], Immunology, Physiology, 010501 environmental sciences, 01 natural sciences, Dermatitis, Atopic, 03 medical and health sciences, 0302 clinical medicine, Settore MED/38 - Pediatria Generale E Specialistica, Food allergy, Pregnancy, Metals, Heavy, medicine, Immunology and Allergy, Humans, 0105 earth and related environmental sciences, Asthma, food allergy, lead, atopic dermatitis, business.industry, Incidence (epidemiology), Hazard ratio, Infant, Atopic dermatitis, asthma, medicine.disease, allergy, Rhinitis, Allergic, 3. Good health, in utero exposure, [SDV] Life Sciences [q-bio], 030228 respiratory system, In utero, Cord blood, Child, Preschool, Pediatrics, Perinatology and Child Health, manganese, Female, eczema, business, Food Hypersensitivity
Abstract: International audience; Background: Accumulating evidence suggests that in utero exposures can influence the development of the immune system and thus contribute to disease development. Studies investigating the association between prenatal exposures to heavy metals and atopic diseases, however, are scarce.Methods: Children from the EDEN birth cohort were prospectively followed up using parental questionnaires with validated questions on asthma, allergic rhinitis, eczema, and food allergy symptoms. The questionnaires were administered every 4 months during the children's first year, and then every year until the age of 5, with a final survey at the age of 8. Serum concentrations of lead (Pb), cadmium (Cd), and manganese (Mn) were assessed in maternal blood samples collected during mid-pregnancy and in cord blood of 651 mother-children pairs. Hazard ratios (HR) for the incidence of each atopic disease in relation to the exposure to metals were calculated using Cox proportional hazard models.Results: Levels of Cd in cord blood were associated with greater risk of asthma (hazard ratio [95% confidence interval] for upper vs lower quartile: 1.81 [1.00-3.29]), eczema (1.60 [1.09-2.35]), and food allergy (3.17 [1.36-7.38]), while Mn levels in maternal serum were associated with eczema (1.55 [1.05-2.28]). These associations were similar in males and females and were confirmed using log concentrations of metals as exposures.Conclusions: Our results support the hypothesis that fetal exposure to heavy metals may affect the development of asthma, eczema, and food allergy in childhood and suggest that timing of exposure in utero may have a role in these associations.
Published: 2020

33. Neurological diseases of unknown etiology: Brain-biopsy diagnostic yields and safety

Author: Bertrand Mathon, Alexandre Le Joncour, Franck Bielle, Karima Mokhtari, Anne-Laure Boch, Matthieu Peyre, Zahir Amoura, Patrice Cacoub, Nadia Younan, Sophie Demeret, Eimad Shotar, Sonia Burrel, Arnaud Fekkar, Jérôme Robert, Aymeric Amelot, Marc Pineton de Chambrun, Alexandre Carpentier, Laurent Capelle, Soledad Navarro, Olivier Benveniste, Dimitri Psimaras, Khê Hoang-Xuan, Jean-Yves Delattre, Nicolas Weiss, Clémence Marois, Sarah Benghanem, Nadine Martin-Duverneuil, Véronique Leblond, Sylvain Choquet, Charles-Edouard Luyt, Alain Combes, Eric Caumes, Vincent Calvez, Aude Jary, Renaud Piarroux, Alexandra Aubry, Vincent Degos, Alice Jacquens, Caroline Papeix, Vincent Navarro, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Neuropathologie [CHU Pitié Salpêtrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Pitié BT, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de virologie [CHU Pitié-Salpêtrière], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière], Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Neurological morbidity, Biopsy, [SDV]Life Sciences [q-bio], Neurosurgery, Neuropathology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Diagnostic workup, Histological diagnosis, Internal medicine, Internal Medicine, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Cryptogenic neurological disease, Retrospective Studies, medicine.diagnostic_test, business.industry, Brain biopsy, Brain, Retrospective cohort study, Odds ratio, 3. Good health, Brain lesion, Etiology, business
Abstract: International audience; Background: For nonneoplastic neurological diseases, no recommendation exists regarding the place or appropriate timing of brain biopsy. The aim of this study was to evaluate the diagnostic yield and safety of brain biopsies from patients with neurological diseases of unknown etiology.Methods: We performed a retrospective cohort study from January 1, 2008 to December 31, 2018. We analyzed 1847 brain-biopsied patients, including 178 biopsies indicated for neurological diseases of unknown etiology. Specific histological and final diagnosis rates, positive diagnosis-associated factors, complication rate and complication-associated factors were assessed.Results: Specific histological diagnosis and final diagnosis rates were 71.3% and 83.1%, respectively, leading to therapeutic management change(s) for 75.3% of patients. Brain- biopsy-related mortality and permanent neurological morbidity occurred in 1.1% and 0.6% of the patients, respectively. The multivariable logistic-regression model retained (odds ratio [95% CI] only immunodepression (2.2 [1.1-4.7]; P=.04) as being independently associated with specific histological diagnosis, while supratentorial biopsy-targeted lesions (4.1 [1.1-15.2]; P=.04) were independently associated with a final diagnosis. Biopsies obtained from comatose patients were less contributive to the diagnosis (0.2 [0.05-0.7]; P=.01). Prebiopsy platelet count
Published: 2020

34. Effect of Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia: A Case-Control Cohort Study

Author: Philippe Zimmermann, Hélène Gros, Arezki Oufella, Helene Guillot, Lee S. Nguyen, Louise Baucher, Louis Dubret, Faiza Boucenna, Paul Barsoum, Benjamin Rossi, Marie Anne Bouldouyre, Yves Allenbach, Joe-Elie Salem, Hôpital Robert Ballanger [Aulnay-sous-Bois], Hôpital Ambroise Paré [AP-HP], Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: medicine.medical_specialty, medicine.medical_treatment, Pharmaceutical Science, lcsh:Medicine, lcsh:RS1-441, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, severe pneumonia, Internal medicine, Drug Discovery, medicine, 030212 general & internal medicine, anti-interleukin-6, Mechanical ventilation, business.industry, SARS CoV2, Hazard ratio, lcsh:R, COVID-19, Retrospective cohort study, cytokine release syndrome, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Confidence interval, respiratory tract diseases, 3. Good health, Pneumonia, chemistry, 030220 oncology & carcinogenesis, Cohort, Molecular Medicine, business, Cohort study
Abstract: Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO2 &le, 96% despite O2-support &ge, 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 0.3&ndash, 0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95%CI = 0.135&ndash, 0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p &lt, 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.
Published: 2020

35. Cardiac sarcoidosis: A long term follow up study

Author: Patrice Cacoub, Matthieu Resche-Rigon, David Saadoun, Lucie Biard, Catherine Chapelon-Abric, Anne Claire Desbois, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Epidemiology, [SDV]Life Sciences [q-bio], Gadolinium, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Gastroenterology, Diagnostic Radiology, Cohort Studies, 0302 clinical medicine, Medical Conditions, Recurrence, Medicine and Health Sciences, 030212 general & internal medicine, Routes of Administration, Multidisciplinary, Ejection fraction, Radiology and Imaging, Drugs, Middle Aged, Prognosis, Magnetic Resonance Imaging, Immunosuppressives, Progression-Free Survival, 3. Good health, Chemistry, Cohort, Physical Sciences, Medicine, Female, Cardiomyopathies, Immunosuppressive Agents, Cohort study, Research Article, Chemical Elements, Adult, medicine.medical_specialty, Paris, Sarcoidosis, Imaging Techniques, Science, Inflammatory Diseases, Cardiology, Lower risk, Research and Analysis Methods, 03 medical and health sciences, Rheumatology, Diagnostic Medicine, Internal medicine, Intravenous Injections, medicine, Humans, Progression-free survival, Survival rate, Cyclophosphamide, Retrospective Studies, Heart Failure, Pharmacology, business.industry, Retrospective cohort study, medicine.disease, Heart failure, Medical Risk Factors, business, Follow-Up Studies
Abstract: BackgroundPrognostic factors are lacking in cardiac sarcoidosis (CS), and the effects of immunosuppressive treatments are unclear.ObjectivesTo identify prognostic factors and to assess the effects of immunosuppressive drugs on relapse risk in patients presenting with CS.MethodsFrom a cohort of 157 patients with CS with a median follow-up of 7 years, we analysed all cardiac and extra-cardiac data and treatments, and assessed relapse-free and overall survival.ResultsThe 10-year survival rate was 90% (95% CI, 84-96). Baseline factors associated with mortality were the presence of high degree atrioventricular block (HR, 5.56, 95% CI 1.7-18.2, p = 0.005), left ventricular ejection fraction below 40% (HR, 4.88, 95% CI 1.26-18.9, p = 0.022), hypertension (HR, 4.79, 95% CI 1.06-21.7, p = 0.042), abnormal pulmonary function test (HR, 3.27, 95% CI 1.07-10.0, p = 0.038), areas of late gadolinium enhancement on cardiac magnetic resonance (HR, 2.26, 95% CI 0.25-20.4, p = 0.003), and older age (HR per 10 years 1.69, 95% CI 1.13-2.52, p = 0.01). The 10-year relapse-free survival rate for cardiac relapses was 53% (95% CI, 44-63). Baseline factors that were independently associated with cardiac relapse were kidney involvement (HR, 3.35, 95% CI 1.39-8.07, p = 0.007), wall motion abnormalities (HR, 2.30, 95% CI 1.22-4.32, p = 0.010), and left heart failure (HR 2.23, 95% CI 1.12-4.45, p = 0.023). After adjustment for cardiac involvement severity, treatment with intravenous cyclophosphamide was associated with a lower risk of cardiac relapse (HR 0.16, 95% CI 0.033-0.78, p = 0.024).ConclusionsOur study identifies putative factors affecting morbidity and mortality in cardiac sarcoidosis patients. Intravenous cyclophosphamide is associated with lower relapse rates.
Published: 2020

36. Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

Author: Jean-Sébastien Hulot, Felix Ackermann, N. Costedoat-Chalumeau, Jérémie Sellam, Amar Smail, Claire Goulvestre, Jean-Emmanuel Kahn, François Chasset, Gaëlle Leroux, Laurent Perard, Patrice Cacoub, Karim Sacre, Du Le Thi Huong, Moez Jallouli, Olivier Fain, Lionel Galicier, Bouchra Asli, Noémie Jourde-Chiche, Michel Vidal, Véronique Le Guern, Frédéric Lioté, Jean-Charles Piette, Judith Cohen-Bittan, Xavier Mariette, O. Aumaître, Thomas Papo, Benoit Blanchet, Marie Allard, Pascale Ghillani-Dalbin, Jérôme Stirnemann, Nicolas Limal, Hélène Desmurs-Clavel, Zahir Amoura, Laurent Sailler, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Chimie médicinale et recherche translationnelle (ERL Inserm U1268), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hedi Chaker Hospital [Sfax], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Tenon [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Hospices Civils de Lyon (HCL), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], Hôpitaux Universitaires de Genève (HUG), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de dermatologie et allergologie [CHU Tenon], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Service de médecine interne [CHU Saint-Antoine], Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Service de rhumatologie [CHU Saint-Antoine], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Purpan [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de gériatrie [CHU Pitié-Salpêtrière], and Gestionnaire, Hal Sorbonne Université
Subjects: Serum, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Systemic lupus erythematosus, Pharmacokinetics, Risk Factors, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, In patient, 030212 general & internal medicine, Whole blood, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Hydroxychloroquine, Drug monitoring, Rheumatology, Non adherence, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Adherence, Pharmacodynamics, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Antirheumatic Agents, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Patient Compliance, lcsh:RC925-935, business, medicine.drug, Research Article
Abstract: Background Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. Methods HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ Results The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76–0.94) and specificity of 0.89 (95% CI 0.72–0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level ( Conclusions These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.
Published: 2020

37. Generation and validation of small ADAMTS13 fragments for epitope mapping of anti‐ADAMTS13 autoantibodies in immune‐mediated thrombotic thrombocytopenic purpura

Author: Gilles Kaplanski, Kadri Kangro, Jan Voorberg, Andres Männik, Karen Vanhoorelbeke, Simon F. De Meyer, Elien Roose, An-Sofie Schelpe, Edwige Tellier, Université Catholique de Louvain = Catholic University of Louvain (UCL), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Amsterdam [Amsterdam] (UvA), Laboratory for Thrombosis Research [Kortrijk, Belgium], KU Leuven Campus Kulak Kortrijk [Belgium], European Project: 675746,H2020,H2020-MSCA-ITN-2015,PROFILE(2015), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Experimental Vascular Medicine, Landsteiner Laboratory, ACS - Microcirculation, AII - Inflammatory diseases, and Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC)
Subjects: EXPRESSION, medicine.drug_class, SPACER, 030204 cardiovascular system & hematology, Monoclonal antibody, Epitope, 03 medical and health sciences, 0302 clinical medicine, DOMAIN, hemic and lymphatic diseases, medicine, antibodies, thrombotic thrombocytopenic purpura, BATCH, 030304 developmental biology, ADAMTS13 protein, 0303 health sciences, Thrombospondin, Science & Technology, PLASMA, biology, lcsh:RC633-647.5, Chemistry, Autoantibody, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, epitopes, GLYCANS, Molecular biology, Fusion protein, ADAMTS13, 3. Good health, Epitope mapping, human serum albumin, ANTIBODIES, biology.protein, SECRETION, Original Article, Antibody, Life Sciences & Biomedicine, Original Articles: Thrombosis
Abstract: BACKGROUND: In immune-mediated thrombotic thrombocytopenic purpura (iTTP), patients develop an immune response against the multidomain enzyme ADAMTS13. ADAMTS13 consists of a metalloprotease (M) and disintegrin-like (D) domain, 8 thrombospondin type 1 repeats (T1-T8), a cysteine-rich (C), a spacer (S), and 2 CUB domains (CUB1-2). Previous epitope mapping studies have used relatively large overlapping ADAMTS13 fragments. OBJECTIVES: We aimed at developing small nonoverlapping ADAMTS13 fragments to fine map anti-ADAMTS13 autoantibodies in iTTP patients. METHODS: A library of 16 ADAMTS13 fragments, comprising several small (M, DT, C, S, T2-T5, T6-T8, CUB1, CUB2), and some larger fragments with overlapping domains (MDT, MDTC, DTC, CS, T2-T8, CUB1-2, MDTCS, T2-C2), were generated. All fragments, and ADAMTS13, were expressed as a fusion protein with albumin domain 1, and purified. The folding of the fragments was tested using 17 anti-ADAMTS13 monoclonal antibodies with known epitopes. An epitope mapping assay using small ADAMTS13 fragments was set up, and validated by analyzing 18 iTTP patient samples. RESULTS: Validation with the monoclonal antibodies demonstrated that single S and CUB1 were not correctly folded, and therefore CS and CUB1-2 fragments were selected instead of single C, S, CUB1, and CUB2 fragments. Epitope mapping of antibodies of patients with iTTP confirmed that 6 nonoverlapping ADAMTS13 fragments M, DT, CS, T2-T5, T6-T8, and CUB1-2 were sufficient to accurately determine the antibody-binding sites. CONCLUSION: We have developed a tool to profile patients with iTTP according to their anti-ADAMTS13 antibodies for a better insight in their immune response. ispartof: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS vol:4 issue:5 pages:918-930 ispartof: location:United States status: published
Published: 2020

38. Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

Author: Victor Judith, Devaux Mathilde, Corre Clémence, Morin Franck, Ebstein Esther, Desmurs Marie, Juillard Laurent, Descamps Elise, Galland Joris, Gahier Penhoat Mélanie, Hellier Jean-Pierre, Mariette Xavier, Poix Elsa, Hudry Christophe, Constant Elodie, Trijau Sophie, Moranne Olivier, Diot Elisabeth, Hie Miguel, Guilpain Philippe, Boussoualim Karima, Mathian Alexis, Pouchot Jacques, Rohmer Julien, Senet Patricia, Michaud Martin, Tieulie Nathalie, Liote Frédéric, Ducornet Angélique, Couret Marie, Revuz Sabine, Morel Hugo, Moly Marie, Direz Guillaume, Milesi-Lecat Anne-Marie, Meinzer Ulrich, Bader-Meunier Brigitte, Steib Sarah, Gauthier-Prieur Maud, Bertolini Ewa, Gombert Bruno, Dumel Anne-Elisabeth, Henriot Basile, Froissart Antoine, Smets Perrine, Robin Sophie, Rousselin Clémentine, Moulinier Laurence, Mazet-Guillaume Betty, Brondino Regine, Malochet-Guinamand Sandrine, Balandraud Nathalie, Gibert Christelle, Godeau Bertrand, Aeschlimann Florence, Bonnet Christine, Plassard Samira, Lebrun Agnès, Mehsen-Cetre Nadia, Arlet Jean-Benoît, Gagneux-Lemoussu Laurence, Kemiche Farid, Michon Mathilde, Szafors Paulina, Werle Claude, Guillaud Constance, La Batide Alanore Sylvain, Borie Raphaël, Chazerain Pascal, Puyraimond-Zemmour Déborah, Barrelet Audre, Bach-Bunner Maxime, Flaisler Françoise, Euvrard Romain, Evon Philippe, Feurer Elodie, Gerard Nathalie, Gervais Elisabeth, Sordet Christelle, Bally Stéphane, Mazouyez Arnaud Angers, Guillot Xavier, Comarmond Chloé, Leloire Olivier, Fauconier Marion, Bouhour Françoise, Woessner Juliette, Jaccard Clara, Langlois Vincent, Sicaud Aurélie, Rolland Michel, Kabala Anna, Atlan Lucie, Amador-Borreiro Blanca, Jan Catherine, Leturcq Tifenn, Gonnet-Gracia Camille, Lanot Sylvain, Hachulla Eric, Bonidan Olivier, Domont Fanny, Dumaine Cécile, Bouiller Kévin, Senbel Eric, Comparon Céline, Huguenel Serge, Despaux Jacques, Roth Olivier, Berthoux Emilie, Dehimat Sarahe, Costedoat-Chalumeau Nathalie, Bayer Guillaume, Melki Isabelle, Toussirot Eric, Buchlin Pierre, Baumier Vincent, Charcot Agnès, Durand Géraldine, Garraud Thomas, Richez Christophe, Gillard Jérôme, Chaigne Benjamin, Rousiere Mickaël, Le Guen Guegan Sophie, Chertok Pascale, Lucas Virginie, Sadji Fatiha, Garnier Nicole, Sailler Laurent, Garrot Jean-François, Taffignon-Clave Séverine, Charles Pierre, Bernoux-Manat Brigitte, Salliot Carine, Fechtenbaum Jacques, Quenet Marion, Le Guenno Guillaume, Lanteri Aurélia, Hermet Marion, Delahousse Michel, Basch André, Grateau Gilles, Chevalier Xavier, Nocturne Gaétane, Schmidt Jean, Pacaud-Vitoux Isabelle, Roumier Mathilde, Rozenberg Sylvie, Veillard Eric, Roux Nicolas, Marhadour Thierry, Colette-Cedoz Marie-Eve, Cohen Gregory, Foltz Violaine, Fouque-Aubert Anne, Havard Marie-Noelle, Molto Anna, Chevreau Maxime, Strotz Victor, Allanore Yannick, Grardel Bruno, Francois-Pradier Hélène, Devauchelle-Pensec Valérie, Hennequin Pascal, Warzocha Ursula, Collercandy Nived, Bayle Sophie, Audren Victor, Virone Alexandre, Bennet Pascal, Grados Franck, Charpin Caroline, Fuzibet Piera, Albert Jean-David, Larbre Jean-Paul, Coutarel Cécile, Nicolas-Vullierme Sabine, Gastaldi Romain, Guyot Marie-Hélène, Georgescu Dana, Clavel Gaëlle, Tison Alice, Viallard Jean-François, Maria Alexandre, Glanowski Camille, Leroux Christophe, Vidon Mathias, Banal Frédéric, Fulpin Jean, Chotard Emilie, Gaud-Listrat Véronique, Jean Sylvie, Seguier Julie, Jacquemier Jean-Michel, Chatelus Emmanuel, Djeddi Djamal-Dine, Contamine-Sur-Arve Mazyad Hassan, Georgin-Lavialle Sophie, Belot Alexandre, Seve Pascal, Willems Alexandra, Moulis Guillaume, Latourte Augustin, Roux Marielle, Bolla Gilles, Renard Myriam, Xerri-Campano Bernadette, Bisson-Vaivre Aurélia, Fichet Amandine, Dufauret-Lombard Carine, Nielly Hubert, Ledoult Emmanuel, Alcais Didier, Giraudet-Le Quintrec Jeanine-Sophie, Wendling Daniel, Govindaraju-Audouard Sophie, Claudepierre Pascal, Fritz Pierre, Fougerousse Anne-Claire, Marotte Hubert, Fabre Sylvie, Banneville Béatrice, Quartier-Dit-Maire Pierre, Juge Pierre-Antoine, Moura Bertrand, Maillet Thibault, Messer Laurent, Thomachot Benoît, Giraud-Morelet Aude, Sparsa Lætitia, Kabchou Abdelkrim, Grasland Anne, Maurier François, Belin Véronique, Grenoble Gimonnet Pauline, Balblanc Jean-Charles, Andre Emma, Veillard Ericveillard Marie-Eliseeric, Chu Miow Lin, Pugnet Grégory, Wisniewski Michel, Carbasse Aurélia, Rene Jessica, Economu-Dubosc Andra, Bouldoires Bastien, Glace Baptiste, Benhamou Mathilde, Legoupil Nathalie, Morel Jacques, Castel Brice, Lafforgue Pierre, Carteni Maurizio, Lohse Anne, Detree Frédérick, Celant Annalisa, Trefond Ludovic, Maillard Hélène, Remy Philippe, Barnetche Thomas, Servettaz Amélie, Vigne Camille, Ferreira-Maldent Nicole, Mangon Quentin, Keraen Jérémy, Fautrel Bruno, Frantzen Léa, Legrand Erick, Sellam Jérémie, Tenenbaum Nora, Sene Thomas, Duc Catherine, Bouvard Eric, Dieudonne Yannick, Ollagnon Henri-Olivier, Deslandre Chantal, Gury Aline, Desplats Marie, Karman Françoise, Drouet Béatrice, Vidon Claire, Kone-Paut Isabelle, Groza Monica, Jamard Bénédicte, Parrot Antoine, Vial Guillaume, Ebbo Mikaël, Ait-Abdallah Nassim, Veillon Laurent, Roriz Mélanie, Chaillous Benoît, Rouidi Sid-Ahmed, Sobanski Vincent, Poulet Antoine, Clavel-Osorio Cyril, Nguyen Minh, Felten Renaud, Goulenok Tiphaine, Audoin-Pajot Christine, Foret Jennifer, Arniaud Denis, Benammar Mohammed, Boudou Laurence, Pascaud-Mansour Yasmina, Pavy Stephan, Sornay-Rendu Elisabeth, Pascart Tristan, Madelon Aurélie, Koreichi Abdeldajallil, Flipo René-Marc, El Mahou Soumaya, Benmansour Ahmed, Arty-Hue Herliette, Pers Yves-Marie, Hittinger-Roux Ambre, Sacco Isabelle, Fernandes Fanny, Gandjbakhch Frédérique, Maury Frédéric, Hacquard-Bouder Cécile, Foutrier-Morello Catherine, Rossi Linda, Belkhir Rakiba, Riviere Etienne, Drumez Elodie, Avouac Jérôme, Benainous Ruben, Champy Romuald, Florens Nans, Pichon Maud, Gibert Eric, Benhamou Ygal, Portier Agnès, Riviere Sébastien, Pham Thao, Blaison Gilles, Colombey Antoine, Marchou-Lopez Sylvie, Roux Fabienne, Leroy Rémi, Lejeune Charlotte, Bacquet-Deschryver Hélène, Romier Mélanie, Simoens Justine, Caumont Hervé, Arnaud Laurent, Paulin Lætitia, Duret Pierre-Marie, Dieude Philippe, Coury-Lucas Fabienne, Pha Micheline, Herasse Muriel, Mahevas Matthieu, Roitg Isabelle, Karkowski Ludovic, Dhote Robin, Chaudier Bernard, Gourmelen Olivier, Trouillier Sébastien, Henry Julien, Daver-Malaterre Laurence, Cathebras Pascal, Goupille Philippe, Seror Raphaële, Thomas Thierry, Pertuiset Edouard, Amoura Zahir, Richard-Colmant Gaëlle, Souchaud-Debouverie Odile, Lahalle Sophie, Jouvray Mathieu, Hentgen Véronique, Courvoisier Natacha, Charlot-Lambrecht Isabelle, Damade Richard, Argenteuil Pizana Gabrielle, Fontanges Elisabeth, Morel Gautier, Roux Christian, Perard Laurent, Gaches Francis, Cacoub Patrice, Mekinian Arsène, Cohen Fleur, Margarit Nathalie, Salmon Jean-Hugues, Guillaume Séverine, Gilson Mélanie, Coutier Fabrice, Rouzaud Diane, Duhamel Alain, Combe Bernard, Jullien Denis, Gill Ghislaine, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Saint-Joseph [Marseille], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPCité Médecine Paris Centre), Université Paris Cité (UPCité), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Necker - Enfants Malades [AP-HP], CH Belfort-Montbéliard, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Avicenne [AP-HP], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], CHU Rouen, Normandie Université (NU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Médecine interne [Hôpitaux civils de Colmar], Hôpitaux Civils de Colmar, Institut national de recherches archéologiques préventives (Inrap), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Cochin [AP-HP], PSA Peugeot Citroën (PSA), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hôpital d'Instruction des Armées Laveran, Service de rhumatologie [Groupe Hospitalier Diaconesses Croix Saint Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation Ophtalmologique Adolphe de Rotschild, Service de Médecine Intensive et Réanimation [Tours], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST, Hôpital Foch [Suresnes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de médecine interne [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de rhumatologie (Hôpitaux Civils de Colmar), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Chimie Agro-Industrielle (CAI), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, CHU Trousseau [Tours], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier de Dax, Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Hôpitaux Privés de Metz (HPMetz), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne [Centre hospitalier Lons le Saunier], Centre hospitalier Lons le Saunier, Service de Rhumatologie [CHU de Grenoble], Hôpital Sud de Grenoble, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], CHU Trousseau [APHP], CHU Amiens-Picardie, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Langues et civilisations à tradition orale (LACITO), Université Sorbonne Nouvelle - Paris 3-Institut National des Langues et Civilisations Orientales (Inalco)-Centre National de la Recherche Scientifique (CNRS), Études Pharmaco-Immunologie (EPI), Université de La Réunion (UR), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, CHU Toulouse [Toulouse], Département de Pédiatrie [Rennes] = Paediatrics [Rennes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Club Rhumatismes et Inflammation, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), CHU Clermont-Ferrand, Université de Lille, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Centre Hospitalier Victor Jousselin de Dreux, Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Belfort (Service de Rhumatologie), Oncology, Regional Hospital of Orleans, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Gabriel Montpied [Clermont-Ferrand], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, CHU Saint-Etienne, Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases [Paris], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Rhumatologie [CHRU Montpellier], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Histoire, Archéologie et Littératures des mondes chrétiens et musulmans médiévaux (CIHAM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-École des hautes études en sciences sociales (EHESS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Columbia University Irving Medical Center (CUIMC), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut du Mouvement et de l'appareil Locomoteur (IML), Service d'Anesthésie réanimation [CHU Tenon], Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Hopital Réné Dubos, Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine interne - hôpital européen Georges-Pompidou, Aix Marseille Université (AMU), Sorbonne Université (SU), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de La Réunion - Faculté de Lettres et Sciences humaines (UR FLSH), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Grenoble Alpes - École supérieure du professorat et de l'éducation - Académie de Grenoble (UGA ESPE Grenoble), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe ENergie Electrique et SYStémique (LAPLACE-GENESYS), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cabinet Médical de Rhumatologie, Marseille, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de dermatologie et allergologie [CHU Tenon], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), FHU 'Integrated center for research in inflammatory diseases - InCREASe', Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Saint-André, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Joseph Ducuing, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire Navier (NAVIER UMR 8205), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], communicable diseases, Disease, Logistic regression, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, Adrenal Cortex Hormones, Epidemiology, Immunology and Allergy, Medicine, 030212 general & internal medicine, 2. Zero hunger, education.field_of_study, glucocorticoids, Mortality rate, tumor necrosis factors, Intensive care unit, 3. Good health, Hospitalization, Autoinflammatory Disorders, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biological therapy, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hypertension, Female, Adult, medicine.medical_specialty, Immunology, Population, imported, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, Rheumatic Diseases, Humans, autoimmune diseases, Obesity, education, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, business, Body mass index
Abstract: ObjectivesThere is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.MethodsIndividuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate–severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.ResultsOf 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05–1.10), female gender (OR=0.45, 95% CI: 0.25–0.80), body mass index (OR=1.07, 95% CI: 1.02–1.12), hypertension (OR=1.86, 95% CI: 1.01–3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09–3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47–29.62) and rituximab (OR=4.21, 95% CI: 1.61–10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87–2.42) (n=175 each group).ConclusionsIn the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.Trial registration numberClinicalTrials.gov Registry (NCT04353609).
Published: 2020

39. Targeting JAK/STAT pathway in Takayasu’s arteritis

Author: David Klatzmann, Anna Maciejewski-Duval, Cloé Comarmond, David Saadoun, Paul Régnier, Alexandre Le Joncour, Michelle Rosenzwajg, A.C. Desbois, Patrice Cacoub, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Adult, Male, Chemokine, MAP Kinase Signaling System, [SDV]Life Sciences [q-bio], Immunology, T cells, chemokines, Lymphocyte Activation, General Biochemistry, Genetics and Molecular Biology, stat, Proinflammatory cytokine, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Downregulation and upregulation, Immunology and Allergy, Medicine, Humans, Janus Kinase Inhibitors, IL-2 receptor, Janus Kinases, 030203 arthritis & rheumatology, biology, business.industry, JAK-STAT signaling pathway, Middle Aged, Th1 Cells, Takayasu Arteritis, cytokines, 3. Good health, STAT Transcription Factors, 030104 developmental biology, inflammation, biology.protein, Cancer research, Th17 Cells, Female, Interferons, systemic vasculitis, business, Janus kinase
Abstract: ObjectiveTakayasu’s arteritis (TAK) is a large vessel vasculitis with important infiltration of proinflammatory T cells in the aorta and its main branches, but its aetiology is still unknown. Our work aims to explore the involvement of Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signalling pathway in proinflammatory T cells differentiation and disease activity of TAK.MethodsWe analysed transcriptome and interferons gene signatures of fluorescence-activated cell sorting (FACS-sorted) CD4+ and CD8+ T cells from healthy donors (HD) and in 25 TAK (median age of 37.6 years including 21 active TAK with National Institutes of Health (NIH) score >1). Then we tested, in vitro and in vivo, the effects of JAK inhibitors (JAKinibs) in TAK.ResultsTranscriptome analysis showed 248 and 432 significantly dysregulated genes for CD4+ and CD8+ samples between HD and TAK, respectively. Among dysregulated genes, we highlighted a great enrichment for pathways linked to type I and type II interferons, JAK/STAT and cytokines/chemokines-related signalling in TAK. We confirmed by Real Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) the upregulation of type I interferons gene signature in TAK as compared with HD. JAKinibs induced both in vitro and in vivo a significant reduction of CD25 expression by CD4+ and CD8+ T cells, a significant decrease of type 1 helper T cells (Th1) and Th17 cells and an increase of Tregs cells in TAK. JAKinibs also decreased C reactive protein level, NIH score and corticosteroid dose in TAK patients.ConclusionsJAK/STAT signalling pathway is critical in the pathogenesis of TAK and JAKinibs may be a promising therapy.
Published: 2020

40. Strategies to prevent persistent or relapsed mixed cryoglobulinemia

Author: David Saadoun, Patrice Cacoub, Gonçalo Boleto, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: business.industry, Health Policy, [SDV]Life Sciences [q-bio], food and beverages, medicine.disease, Cryoglobulinemia, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Immune system, 030220 oncology & carcinogenesis, hemic and lymphatic diseases, Mixed cryoglobulinemia, Immunology, medicine, Pharmacology (medical), Rituximab, business, Vasculitis, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Cryoglobulinemic vasculitis, 030217 neurology & neurosurgery, medicine.drug, Systemic vasculitis
Abstract: International audience; Mixed cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification.
Published: 2020

41. Screening coronary artery disease with computed tomography angiogram should limit normal invasive coronary angiogram, regardless of pre-test probability. Short title: coronary artery disease screening with CTscan

Author: Houssany-Pissot, Sonia, Rosencher, Julien, Allouch, Philippe, Bensouda, Christophe, Pillière, Remy, Cacoub, Léa, Caussin, Christophe, El-Hadad, Simon, Makowski, Serge, Beverelli, Fabrizio, Cacoub, Patrice, Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut Mutualiste de Montsouris (IMM), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: functional testing, invasive coronary angiogram, computed tomography coronary angiogram, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, coronary artery disease
Abstract: International audience; BackgoundPerforming functional testing (FT) or a computed tomography angiogram (CCTA) before invasive coronary angiogram (ICA) is recommended for coronary artery disease (CAD). We aimed to evaluate, in a real life setting, the rate of strictly normal ICA following a positive noninvasive test result.MethodsWe included all patients who underwent an ICA with a prior positive FT or CCTA. Patients were categorized in 5 subgroups, according to pretest probability (PTP) of having a CAD. Main results of ICA were defined as normal ICA, nonobstructive CAD (non-oCAD), and obstructive CAD (oCAD).ResultsFor 4,952 patients who underwent ICA following either a positive FT (3276, 66.2%) or CCTA (1676, 33.8%) result, the PTP was (1) low ( 65%; n = 965, 19.5%). ICA showed no CAD (819 patients, 16.5%), non-oCAD (1,193 patients, 24.1%), or oCAD (2940 patients, 59.4%). Without considering the PTP values, CCTA compared to FT showed less frequently normal ICA (7% vs 16.5%), and more frequently CAD (non-oCAD 27.9% vs 22.2%; oCAD 65.1% vs 56.4%) (all P
Published: 2020

42. HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma

Author: Sonigo, Gabrielle, Battistella, Maxime, Beylot-Barry, Marie, Ingen-Housz-Oro, Saskia, Franck, Nathalie, Barète, Stéphane, Boulinguez, Serge, Dereure, Olivier, Bonnet, Nathalie, Brice, Pauline, Boccara, Olivia, Bodemer, Christine, Adamski, Henri, D'Incan, Michel, Ortonne, Nicolas, Fraitag, Sylvie, Brunet-Possenti, Florence, Dalle, Stéphane, Suarez, Felipe, Skowron, François, Haidar, Dima, Maubec, Eve, Bohelay, Gerome, Laroche, Liliane, Mahé, Antoine, Birckel, Elodie, Bouaziz, Jean-David, Brocheriou, Isabelle, Dubois, Romain, Faiz, Sarah, Fadlallah, Jehane, Ram-Wolff, Caroline, Carlotti, Agnès, Bens, Guido, Balme, Brigitte, Vergier, Béatrice, Laurent-Roussel, Sara, Deschamps, Lydia, Carpentier, Olivier, Moguelet, Philippe, Herve, Genevieve, Comoz, Francois, Le Gall, François, Leverger, Guy, Finon, Antoine, Augereau, Olivier, Blechet, Claire, Kerdraon, Rémy, Lamant, Laurence, Tournier, Emilie, Franck, Frédéric, Costes-Martineau, Valérie, Szablewski, Vanessa, Taix, Sebastien, Beschet, Isabelle, Guérin, Frédéric, Sepulveda Garrido, Fernando, Bagot, Martine, De Saint Basile, Geneviève, Michonneau, David, de Masson, Adèle, Socié, Gérard, Bodemer, Shristine ChB, Marçais, Ambroise, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Henri Mondor, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Hôpital Nord [CHU - APHM], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre Hospitalier de Valence (CH DE VALENCE), Centre hospitalier de Valence, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Avicenne [AP-HP], Hôpital pasteur [Colmar], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Mouvement, Équilibre, Performance, Santé (MEPS), Université de Pau et des Pays de l'Adour (UPPA), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service de pathologie [CHU Bichat], Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire d'aérologie (LAERO), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre Hospitalier Régional d'Orléans (CHR), Laboratoire d'aérologie (LA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunithérapie (HIPI (UMR_S_976 / U976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Anatomie et cytologie pathologiques [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COLO, Mouniati, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.medical_specialty, Panniculitis, [SDV]Life Sciences [q-bio], Immunology, 2 supplemental tables, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymphoma, T-Cell, HAVCR2, Biochemistry, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Subcutaneous Panniculitis-Like T-Cell Lymphoma, 9 references Article type: Letter Scientific category: Lymphoma, Humans, Medicine, Genetic Predisposition to Disease, Hepatitis A Virus Cellular Receptor 2, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Hemophagocytic lymphohistiocytosis, business.industry, Cell Biology, Hematology, medicine.disease, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], 1 supplemental figure, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), 2 tables, Female, business, Biomarkers
Abstract: International audience
Published: 2020

43. Recovering autonomy is a key advantage of home-based immunoglobulin therapy in patients with myositis A qualitative research study

Author: Jean-Charles Crave, Martin Duracinsky, Patrick Cherin, Taylor Pindi Sala, Pierre Clerson, Olivier Chassany, Annaïk Dokhan, Yann Fardini, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Male, Pediatrics, [SDV]Life Sciences [q-bio], Self Administration, Single Center, Polymyositis, in-depth interviews, 0302 clinical medicine, Quality Improvement Study, 030212 general & internal medicine, preference, Qualitative Research, Myositis, Aged, 80 and over, General Medicine, Focus Groups, Middle Aged, 3. Good health, Treatment Outcome, textual analysis, 030220 oncology & carcinogenesis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, focus group, Female, medicine.symptom, Self-administration, Research Article, Adult, medicine.medical_specialty, Injections, Subcutaneous, Immunoglobulins, Dermatomyositis, Drug Administration Schedule, 03 medical and health sciences, Refractory, patients’ expectations, medicine, Humans, autonomy, Aged, business.industry, Immunization, Passive, Muscle weakness, medicine.disease, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Qualitative research
Abstract: Supplemental Digital Content is available in the text, Immunoglobulins are 2nd or 3rd-line treatments in dermatomyositis (DM) or polymyositis (PM) refractory to high-dose corticosteroids and immunosuppressants. Immunoglobulins (2 g/kg/mo) are usually administered intravenously (IVIg) once a month and the patients stay at hospital for a few days. Recently, subcutaneous injections (SCIg) were proposed 2 to 3 times per week, in some dysimmune diseases. SCIg are administered at home preferably by the patient or by a nurse. We investigated the needs and attitudes of DM and PM patients with experience of IVIg and SCIg. Seven patients (6 PM and 1 DM) from a single center participated in a focus group (N = 6) or underwent in-depth interview (N = 1). Six had the experience of both IVIg at hospital and SCIg at home; 1 has received only IVIg at hospital. Verbatim was recorded and transcribed for further content analysis and computer-aided textual analysis. Clinical profiles and stories were heterogeneous. At diagnosis, muscle weakness, severe pain, and fatigue were at the forefront of patients’ complaints impairing daily life. Patients reported considerable improvement with immunoglobulins. SCIg were described as easy, less disruptive for daily life, well tolerated, and less time-consuming. SCIg self-administration at home restored the feeling of autonomy and control. Interviews of DM and PM patients revealed that recovering autonomy and control was a central advantage of home-based SCIg that were efficient, well tolerated, and perceived as a good compromise between treatment burden and efficacy.
Published: 2020

44. Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy

Author: Olivier Benveniste, Varun K. Sharma, Maxime Lecerf, Anupama Karnam, Emmanuel Stephen-Victor, Bharat Bhatt, Fabian Käsermann, Veerupaxagouda Patil, Kithiganahalli Narayanaswamy Balaji, Jagadeesh Bayry, Naresh Rambabu, Srini V. Kaveri, Mrinmoy Das, Laurent Gilardin, Patrick Bruneval, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Microbiology and Cell Biology [Bangalore, India], Université Paris Descartes - Paris 5 (UPD5), CSL Behring, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche en myologie, Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immuno-pathologie et immuno-intervention thérapeutique = Immunopathology and Therapeutic Immuno-intervention [CRC], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Indian Institute of Science [Bangalore] (IISc Bangalore), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), CLS Behring AG, Bern, Service d'Anatomie et de Cytologie Pathologique (SACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Jagadeesh, Bayry, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Thérapie des maladies du muscle strié, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)
Subjects: Lipopolysaccharides, Cancer Research, medicine.medical_treatment, Anti-Inflammatory Agents, Autoimmunity, medicine.disease_cause, p38 Mitogen-Activated Protein Kinases, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Monocytes, 0302 clinical medicine, hemic and lymphatic diseases, Phosphorylation, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Microbiology & Cell Biology, 0303 health sciences, biology, lcsh:Cytology, TOR Serine-Threonine Kinases, Immunoglobulins, Intravenous, Endocytosis, Tissue Donors, 3. Good health, [SDV.IMM]Life Sciences [q-bio]/Immunology, Beclin-1, Immunotherapy, Antibody, [SDV.IMM] Life Sciences [q-bio]/Immunology, p38 mitogen-activated protein kinases, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, Cell Line, Proinflammatory cytokine, Immunoglobulin Fab Fragments, 03 medical and health sciences, Cellular and Molecular Neuroscience, Immune system, Autophagy, medicine, Humans, lcsh:QH573-671, 030304 developmental biology, Organelles, Innate immune system, business.industry, Macrophages, Adenylate Kinase, Dendritic Cells, Cell Biology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Translational research, Immunity, Innate, Leukocytes, Mononuclear, biology.protein, Phosphatidylinositol 3-Kinase, business, 030215 immunology
Abstract: Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab′)2-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases.
Published: 2020

45. Routine monitoring of isometric knee extension strength in patients with muscle impairments using a new portable device: cross-validation against a standard isokinetic dynamometer

Author: Jean-Yves Hogrel, Olivier Benveniste, Damien Bachasson, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP]
Subjects: Muscle Strength Dynamometer, Weakness, Knee Joint, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physiology, Biomedical Engineering, Biophysics, Isometric exercise, Cross-validation, Myositis, Inclusion Body, 03 medical and health sciences, outcome measures, Wearable Electronic Devices, 0302 clinical medicine, [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Physiology (medical), Isometric Contraction, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Humans, Muscle Strength, device, muscle weakness, Aged, Reproducibility, Dynamometer, business.industry, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 030229 sport sciences, Gold standard (test), Middle Aged, Standard error, medicine.symptom, business, myositis, 030217 neurology & neurosurgery, Biomedical engineering
Abstract: International audience; OBJECTIVE: Muscle strength is a critical clinical hallmark in both health and disease. The current study introduces a novel portable device prototype (MyoQuad) for assessing and monitoring maximal voluntary isometric knee extension torque (MVIT).APPROACH: Fifty-six patients with inclusion body myositis were studied. Knee extension weakness is a key feature in this inflammatory muscle disease. Cross-validation with an isokinetic dynamometer (Biodex System 3 Pro) was performed. Between-day reproducibility and ability to monitor changes in muscle strength over time compared to the gold standard method as a reference, were also investigated.MAIN RESULTS: The measurement was feasible even in the weakest patients. Agreement between methods was excellent (standard error of measurement (SEM) was 3.8 Nm and intra-class correlation coefficient (ICC) was 0.973). Least significant difference (LSD) was 4.9 and 5.3 Nm for the MyoQuad and the Biodex, respectively Measurements using the MyoQuad exhibited excellent between-day reproducibility (SEM was 2.4 Nm and ICC was 0.989 versus 2.6 Nm and 0.988 using the Biodex). Changes in MVIT at 6 and 12 months were similar between methods (timepoint × method interaction was not significant; all p > 0.19); strength changes classified according to LSD at 6 and 12 months were consistent between methods (>70% consistent classification)).SIGNIFICANCE: The measurement of MVIT using the MyoQuad offers a cost-effective, portable and immediate alternative for the routine measurement of maximal voluntary isometric strength of the quadriceps. The MyoQuad offers a comfort and stability that cannot be provided by standard hand-held dynamometers. These results support quantitative muscle strength assessment using fixed yet flexible dynamometry within clinical routine and multicenter trials.
Published: 2020

46. Tocilizumab in treatment-naïve patients with Takayasu arteritis: TOCITAKA French prospective multicenter open-labeled trial

Author: Jean Pierre Bertola, Léa Savey, Juliette Delforge, David Saadoun, Patrick Jego, Olivier Fain, Matthieu Vautier, Pauline Lhorte, Nicole Ferreira-Maldent, Patrice Cacoub, Arsène Mekinian, Jérôme Connault, Jacques-Eric Gottenberg, Nicolas Limal, Bertrand Lioger, Zohra Talib, Eric Vicaut, Sara Thietart, Isabelle Quiere, Alexandre Bleibtreu, Antoinette Perlat, Gestionnaire, Hal Sorbonne Université, Service de médecine interne [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Saint-Antoine], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Hôpital Jean Verdier [AP-HP], CHU Henri Mondor, Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Adult, musculoskeletal diseases, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, [SDV]Life Sciences [q-bio], Takayasu arteritis, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Gastroenterology, Therapy naive, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Maintenance therapy, Internal medicine, medicine, Clinical endpoint, Humans, Prospective Studies, skin and connective tissue diseases, 030203 arthritis & rheumatology, business.industry, Rheumatology, 3. Good health, Discontinuation, [SDV] Life Sciences [q-bio], Treatment Outcome, chemistry, Orthopedic surgery, Female, lcsh:RC925-935, business, Vasculitis treatment, Research Article
Abstract: Objectives To assess long-term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK). Methods Prospective open-labeled trial in naïve patients with TAK who received steroids at the dose of 0.7 mg/kg/day and 7 infusions of 8 mg/kg/month of tocilizumab. The primary endpoint was the number of patients who discontinued steroids after 7 infusions of tocilizumab. Secondary endpoints included disease activity and the number of relapses during 18-month follow-up. Results Thirteen patients with TAK were included, with a median age of 32 years [19–45] and 12 (92%) females. Six (54%) patients met the primary end-point. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3, 4] at baseline, versus 1 [0–2] after 6 months; p p = 0.002), and ITAS-A score (7 [4–10] versus 4 [1–15]; p = 0.0001)]. During the 12-month follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab. Conclusion Tocilizumab seems an effective steroid sparing therapy in TAK, but maintenance therapy is necessary. Trial registration ClinicalTrials.gov NCT02101333. Registered on 02 April 2014.
Published: 2020

47. Hepatitis C virus-related vasculitis

Author: Matheus Vieira, David Saadoun, Gonçalo Boleto, Patrice Cacoub, HAL-SU, Gestionnaire, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: hepatitis C virus, Hepatitis C virus, Population, medicine.disease_cause, vasculitis, cryoglobulinemia, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, education, Cryoglobulinemic vasculitis, pathophysiology, 030203 arthritis & rheumatology, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, treatment, business.industry, Gastroenterology, medicine.disease, Cryoglobulinemia, Hepatitis C, 3. Good health, Chronic infection, Immunology, Rituximab, business, Vasculitis, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Systemic vasculitis, medicine.drug
Abstract: International audience; Cryoglobulinemic vasculitis (CryoVas) is a small-to-medium vessel systemic vasculitis caused by the deposition of mixed cryoglobulins and immune complexes. Clinical spectrum of CryoVas ranges from mild symptoms to vasculitis involving multiple organs that may progress to more life-threatening ilness. Hepatitis C virus (HCV) chronic infection is the most frequent condition to be assessed in patients with CryoVas. The mortality rate among patients with HCV-associated CryoVas is 3× that of the general population, with a 63% 10-year survival rate. The recent advent of interferon-free direct-acting antivirals (DAAs), which have the potential to induce sustained virological response rates greater than 95%, has dramatically changed the management of chronic HCV infection and HCV-related CryoVas. B-cell depleting strategies, mainly with rituximab, are the main therapeutic option in severe and refractory cases of HCV-associated CryoVas. Despite the progress in the last years on the management of chronic HCV infection, there are still unmet needs regarding therapeutic management of severe and refractory HCV-associated CryoVas.
Published: 2020

48. Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals

Author: Cloé Comarmond, David Saadoun, Patrice Cacoub, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Hepatitis C virus, [SDV]Life Sciences [q-bio], Review, medicine.disease_cause, Asymptomatic, Gastroenterology, Cryoglobulins, cryoglobulinemia, vasculitis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Membranoproliferative glomerulonephritis, Medicine, lcsh:RC799-869, direct-acting antivirals, 030304 developmental biology, 0303 health sciences, treatment, business.industry, Hepatitis C, medicine.disease, Cryoglobulinemia, 3. Good health, [SDV] Life Sciences [q-bio], HCV, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, medicine.symptom, business, Vasculitis, Systemic vasculitis
Abstract: International audience; Hepatitis C virus (HCV) infection is responsible for both hepatic and extrahepatic manifestations. Before the era of direct-acting antivirals (DAA), cryoglobulinemia was related to HCV infection in 70-90% of cases. Observed in 30% to 40% of patients with hepatitis C, mixed cryoglobulinemia is mainly asymptomatic. Conversely, symptomatic cryoglobulinemia vasculitis (CV) can occur in 5-10% of patients with HCV-associated cryoglobulinemia. CV is a small-vessel systemic vasculitis, and organ damage results from circulation and precipitation of cryoglobulins and complement activation. A wide range of clinical symptoms can be observed during CV, and manifestations are potentially life-threatening. The most frequent manifestations occurring in CV are cutaneous, with recurrent purpura, articular with joint pains, neurologic with peripheric neuropathy, and renal with membranoproliferative glomerulonephritis. DAA have drastically changed chronic HCV therapy. DAA induce sustained virological response (SVR) rates greater than 95%, and also improve extrahepatic manifestations such as CV. We review recent studies investigating the clinical and immune effects of DAA therapy on HCV-CV.
Published: 2020

49. Immunomodulatory role of Interleukin-33 in large vessel vasculitis

Author: Aurélie S. Leroyer, Jean-Marie Launay, Marlène Garrido, Gilles Kaplanski, A.C. Desbois, Philippe Cluzel, Michel Arock, Anna Maciejewski-Duval, Cloé Comarmond, Stéphane Barete, Michelle Rosenzwajg, David Klatzmann, Ulrich Blank, Fabien Koskas, Patrice Cacoub, Edwige Tellier, Pierre Fouret, David Saadoun, Patrick Bruneval, Mohamed Jarraya, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Gestionnaire, Hal Sorbonne Université, Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), École normale supérieure - Cachan (ENS Cachan), Faculte de Medecine Xavier Bichat, Université Paris Diderot - Paris 7 (UPD7), Leroyer, Aurelie, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], DIGNAT-GEORGE, Françoise, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP]
Subjects: Male, 0301 basic medicine, T cell, [SDV]Life Sciences [q-bio], Giant Cell Arteritis, lcsh:Medicine, Inflammation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, Flow cytometry, 03 medical and health sciences, Th2 Cells, 0302 clinical medicine, Large vessel vasculitis, medicine, Humans, Mast Cells, lcsh:Science, Receptor, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, 030203 arthritis & rheumatology, Multidisciplinary, medicine.diagnostic_test, business.industry, Interleukins, lcsh:R, Interleukin-33, Acquired immune system, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, 3. Good health, Interleukin 33, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immunology, lcsh:Q, Female, medicine.symptom, business, Vasculitis, Cell signalling
Abstract: The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-β within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.
Published: 2020

50. Acute recurrent pericarditis: from pathophysiology towards new treatment strategy

Author: Patrice Cacoub, Cindy Marques, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: 030204 cardiovascular system & hematology, Risk Assessment, interleukin 1, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, recurrent pericarditis, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adrenal Cortex Hormones, Recurrence, Risk Factors, medicine, Humans, Pericarditis, 030212 general & internal medicine, Anakinra, Aspirin, treatment, business.industry, Autoantibody, Inflammasome, autoimmune, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Acquired immune system, 3. Good health, Rilonacept, Clinical trial, Canakinumab, Treatment Outcome, Immunology, autoinflammatory, Cardiology and Cardiovascular Medicine, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; Acute idiopathic or so-called viral pericarditis is a frequent and usually benign disease, although recurrences are frequent. Data strongly suggest the presence of underlying autoinflammatory and/or autoimmune disorders. It has been reported that there is an inflammatory response of the innate immune system typical of ‘autoinflammatory diseases’, predominantly mediated by interleukin-1 (IL-1). This may result from the activation of the inflammasome by a cardiotropic virus or a non-specific agent. The inflammatory response of the adaptive immune system, typical of ‘autoimmune diseases’—mainly mediated by autoantibodies or autoreactive T lymphocytes—seems also involved as anti-heart or anti-intercalated disk autoantibodies were associated with a higher number of recurrences and hospitalisations. Current guidelines recommend that aspirin/non-steroidal anti-inflammatory drugs for a few weeks should be associated to colchicine for 6 months in recurrent pericarditis. In refractory cases, low-dose corticosteroids or immunosuppressive drugs have been proposed with limited efficacy. Growing evidences suggest a place of IL-1 receptor antagonists in the treatment of recurrent pericarditis. Many retrospective studies, one recent randomised placebo-controlled study and data of a real-life large international registry showed the good efficacy of anakinra with a good safety profile. Other IL-1 receptor antagonists showed promising results (canakinumab, rilonacept). However, IL-1 receptor antagonists’ position in the treatment algorithm of recurrent pericarditis needs further evaluation in larger prospective clinical trials to replicate initial findings as well as to assess safety, cost-effectiveness and long-term efficacy.
Published: 2020

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