Author: "Michel, Geneviève" / Topic: 03 medical and health sciences - Searchworks@Jio Institute Digital Library Search Results

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92 results on '"Michel, Geneviève"'

1. Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjogren's syndrome

Author: Marie Wahren-Herlenius, Xavier Mariette, Jacques-Eric Gottenberg, Manuel Ramos-Casals, Chiara Baldini, Aike A. Kruize, Bei Xu, Virginia Fernandes Moça Trevisani, Gabriela Hernández-Molina, Jorge Sanchez-Guerrero, Pilar Brito-Zerón, Sung-Hwan Park, Sandra Gofinet Pasoto, Valeria Valim, Roberto Giacomelli, Roberta Priori, Kathy L. Sivils, Maureen Rischmueller, Wan-Fai Ng, Margit Zeher, Damien Sène, Berkan Armagan, Yasunori Suzuki, Valérie Devauchelle-Pensec, Marika Kvarnström, Soledad Retamozo, Guadalupe Fraile, Gunnel Nordmark, Sonja Praprotnik, Luca Quartuccio, Jacques Morel, Piotr Wiland, David A. Isenberg, Astrid Rasmussen, Seung-Ki Kwok, Stefano Bombardieri, Salvatore De Vita, Hendrika Bootsma, Benedikt Hofauer, Tamer A. Gheita, Thomas Mandl, Fabiola Atzeni, Xiaomei Li, Michele Bombardieri, Daniel Hammenfors, Antonina Minniti, Nihan Acar-Denizli, Roberto Gerli, Roser Solans, Levent Kilic, Eefje van der Heijden, Pulukool Sandhya, Hideki Nakamura, Raphaèle Seror, Debashish Danda, Ildikó Horváth, C. Vollenweider, Hospital Clinic (IDIBAPS), Mimar Sinan Üniversitesi, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], University of Debrecen [Hungary], Oklahoma Medical Research Foundation (OMRF), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Departement of Rheumatology and Immunology, Hefei (Anhui Provincial Hospital), Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Department of Clinical Immunology and Rheumatology, Vellore (Christian Medical College & Hospital), Rheumatology Clinic, Udine (DSMB), UO Complessa Reumatologia, Rome, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Hacettepe University = Hacettepe Üniversitesi, University Medical Center [Utrecht], Division of Rheumatology, Seoul (Department of Internal Medicine), Unit of Experimental Rheumatology, Stockhom (Department of Medicine), University Medical Center, Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University and Azienda Ospedaliera of Perugia, Vall d'Hebron University Hospital [Barcelona], The Queen Elizabeth Hospital, Adelaide, Department of Rheumatology, Skane University Hospital, Division of Rheumatology Kanazawa University Graduate School of Medicine, Kanazawa, Centre for Rheumatology - London, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, Wroclaw Medical University, Uppsala University, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), University of Groningen [Groningen], Department of Immunology and Rheumatology, Nagasaki, Japan, University of L'Aquila [Italy] (UNIVAQ), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), University of Freiburg [Freiburg], Queen Mary University London, Federal University of Sao Paulo (Unifesp), University of Bergen (UiB), Rheumatology Division, Hospital das Clinicas, Sao Paulo (HCFMUSP), Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Rheumatology Department, Cairo, Messina and Milan Univ, Milan, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Rheumatology, Buenos Aires, Department of Immunology [Debrecen, Hungary], Clinical Immunology & Rheumatology, Vellore, Department of Medical Area, University Hospital Santa Maria della Misericordia, Udine, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Physics Department,Rome University 'LaSapienza' (Physics Department,Rome University 'LaSapienza'), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Immunology [Mexico City], Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Rheumatology, Hacetttepe University Faculty of Medicine, Ankara, Laboratoire d'Immunologie [AP-HP Hôpital Kremlin-Bicêtre] (GHU Paris-Sud), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Translational Immunology Groningen (TRIGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Wrocław Medical University, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Universidad de Córdoba = University of Córdoba [Córdoba], Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), and Michel, Geneviève
Subjects: Male, Systemic disease, [SDV]Life Sciences [q-bio], Disease, primary Sjogren's syndrome, Severity of Illness Index, DISEASE, Cohort Studies, geoepidemiology, 0302 clinical medicine, Epidemiology, gender, Medicine, VASCULITIS, CRITERIA, Pharmacology (medical), Registries, African american, 0303 health sciences, Hispanic or Latino, ethnicity, phenotype, primary Sjögren's syndrome, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Sjogren's Syndrome, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Vasculitis, musculoskeletal diseases, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, education, primary Sjögren’s syndrome, DIAGNOSIS, White People, CLASSIFICATION, ethnicity, gender, geoepidemiology, phenotype, primary Sjögren’s syndrome, 03 medical and health sciences, Asian People, Rheumatology, Internal medicine, SCORE, Humans, COHORT, Rheumatology and Autoimmunity, 030304 developmental biology, 030203 arthritis & rheumatology, Reumatologi och inflammation, Information Dissemination, business.industry, MORTALITY, Racial Groups, GEOEPIDEMIOLOGY, AIR-POLLUTION, medicine.disease, Black or African American, Clinical research, Sjogren s, business
Abstract: Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.
Published: 2020

2. Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients

Author: Zuzanna Makowska, Ricard Cervera, Lorenzo Beretta, László Kovács, Marta E. Alarcón-Riquelme, Guillermo Barturen, Isabel Almeida, Divi Cornec, Javier Martín, Jacques-Olivier Pers, Ellen De Langhe, Nicolas Hunzelmann, Carlo Chizzolini, Maria Gerosa, Martin Kerick, Ralf Lesche, Chiara Bellocchi, Barbara Vigone, Rafaela Ortega Castro, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre for Genomics and Oncological Research Pfizer [Granada, Spain], Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Università degli Studi di Milano = University of Milan (UNIMI), Universitätsklinikum Köln (Uniklinik Köln), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Department of Clinical Sciences and Community Health [Milan, Italy], Hospital Clinic, IDIBAPS, Universidad de Barcelona, Ciberes, Barcelona, Spain., Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, University of Szeged [Szeged], CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital Universitaire de Genève, Geneva, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Bayer Pharma AG [Berlin], Instituto de Parasitología y Biomedicina 'López-Neyra', PRECISESADS SSc substudy group, PRECISESADS Flow Cytometry study group : Doreen Belz, Eduardo Collantes-Estevez, Francesca Ingegnoli, Yolanda Jimenez Gómez, Chary Lopez Pedrera, Rik Lories, Gaia Montanelli, Silvia Piantoni, Ignasi Rodriguez Pinto, Carlos Vasconcelos, Christophe Jamin, Concepción Marañón, Lucas Le Lann, Quentin Simon, Bénédicte Rouvière, Nieves Varela, Brian Muchmore, Aleksandra Dufour, Montserrat Alvarez, Jonathan Cremer, Nuria Barbarroja, Velia Gerl, Laleh Khodadadi, Qingyu Cheng, Anne Buttgereit, Aurélie De Groof, Julie Ducreux, Elena Trombetta, Tianlu Li, Damiana Alvarez-Errico, Torsten Witte, Katja Kniesch, Nancy Azevedo, Esmeralda Neves, Sambasiva Rao, Pierre-Emmanuel Jouve., Michel, Geneviève, University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], University of Milan, University Hospitals Leuven and Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium, Università degli Studi di Milano [Milano] (UNIMI), Universidad de Córdoba [Cordoba]-Hospital Universitario Reina Sofía, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Genève, and European Commission
Subjects: MESH: Interferon Type I, MESH: Signal Transduction, Male, 0301 basic medicine, Microarray, systemic sclerosis, Autoimmunity, Diseases, Pathogenesis, DISEASE, MESH: Scleroderma, Systemic, Cohort Studies, Transcriptome, 0302 clinical medicine, Immunophenotyping, Platelet degranulation, Gene expression, MESH: Sequence Analysis, RNA, Immunology and Allergy, Medicine, RNA-Seq, MESH: Cohort Studies, GENE-EXPRESSION, MESH: Aged, MESH: Middle Aged, Toll-Like Receptors, Middle Aged, 3. Good health, Europe, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, epidemiology, Life Sciences & Biomedicine, MESH: Toll-Like Receptors, Signal Transduction, Adult, MESH: Immunophenotyping, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Context (language use), Systemic Sclerosis, Computational biology, General Biochemistry, Genetics and Molecular Biology, MESH: Gene Expression Profiling, 03 medical and health sciences, Rheumatology, MESH: Autoimmunity, Humans, autoimmune diseases, Gene, Aged, 030203 arthritis & rheumatology, Science & Technology, MESH: Humans, Scleroderma, Systemic, Sequence Analysis, RNA, business.industry, MESH: Transcriptome, Gene Expression Profiling, RNA, MESH: Adult, Microarray Analysis, Expressió gènica, MESH: Male, MESH: Microarray Analysis, Scleroderma (Disease), 030104 developmental biology, MESH: Genome-Wide Association Study, MESH: Europe, Esclerodèrmia, business, MESH: Female, Genome-Wide Association Study
Abstract: Objectives: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations. Methods: Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. Results: Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples. Conclusions: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc., This work was supported by eU/eFPia/innovative Medicines initiative Joint Undertaking PrecisesaDs Grant no. 115 565.
Published: 2020

3. Basic Immunology

Author: Jacques-Olivier Pers, Panayiotis G. Vlachoyiannopoulos, Evangelia Zampeli, Haralampos M. Moutsopoulos, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), University of Athens Medical School [Athens], Bioclinic General Hospital of Athens and Institute for Autoimmune Systemic and Neurological Disorders, Athens, Greece, Academy of Athens, Michel, Geneviève, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, 3. Good health, 030304 developmental biology
Abstract: International audience; Immune system provides the mechanisms for attacking foreign invaders, eliminating autologous toxic substances and offering self-tolerance. A reductionist approach of the immune system components and their interactions as provided in this chapter will offer knowledge important to better understand the core mechanisms of autoimmune diseases and design therapies targeting their pathogenic mechanisms. Immunity is divided into (a) innate (or natural), implemented by macrophages, dendritic cells, granulocytes (neutrophils, basophils, and eosinophils), natural killer cells, the complement system, and the acutephase proteins, and (b) adaptive, implemented by B and T cells. Immune cells express sensors on cytoplasmic or endosomal membranes or in the cytoplasm, called “pathogen-associated molecular pattern receptors” (PAMPRs), also called pattern recognition receptors (PRRs), and damage-associated molecular pattern receptors (DAMPRs) to sense foreign invaders or damaged tissues and provide defense against them. Natural immunity cells provide the fjrst line of defense, usually successful in eliminating pathogens, but also they limber up the adaptive immune system to take action in case of any failure of defense. The sensors of B and T cells are their antigen receptors (membrane immunoglobulins and T-cell receptors, respectively) which are dissimilar to each other in terms of specificity; each receptor recognizes very specifically one antigen and especially a few peptide residues on it (epitope). However, by taking as a whole the pool of lymphocytes, their receptors offer a vast array of specificities exceeding 1011 that is more than the genes of the human body. This implies that not particular genes but rather gene fragments are spontaneously rearranged to make an immunoglobulin or a T-cell receptor gene. One such rearrangement for each peptide chain of the receptor is allowed, so the cells will retain their antigenic specificity as long as they live. Immune cells communicate with each other and approach their targets, either by cell-to-cell contact using adhesion molecules or by soluble mediators known as cytokines or chemokines, respectively. Mechanisms like central (taking place in bone marrow and thymus) and peripheral (taking place in the lymph nodes) tolerance ensure that the immune system will not attack self. Braking of tolerance initiates autoimmune reactivity which may be subclinical but, under certain circumstances, may obtain a clinical phenotype.
Published: 2021

4. Practical management of patients on Janus kinase inhibitor (JAKi) therapy: Practical fact sheets drawn up by the Rheumatism and Inflammation Club (CRI), a group endorsed by the French Society for Rheumatology (SFR)

Author: Claire Daïen, Anne Tournadre, Victor de Lédinghen, Thao Pham, Marie-Elise Truchetet, Clément Prati, Thierry Lequerré, Christophe Richez, Gaetane Nocturne, Jean Sibilia, Benoit Le Goff, Raphaèle Seror, Jacques Morel, Valérie Pourcher, Philippe Goupille, Estibaliz Lazaro, Divi Cornec, Rhumatologie Bordeaux (SERVICE DE RHUMATOLOGIE), CHU Bordeaux [Bordeaux], Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Haut-Lévêque [CHU de Bordeaux], Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service des maladies infectieuses et tropicales [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), Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Rhumatologie [CHU Sainte Marguerite], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Michel, Geneviève
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Rheumatic Diseases, Internal medicine, Humans, Janus Kinase Inhibitors, Medicine, Societies, Medical, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Janus kinase inhibitor, Inflammation, 030203 arthritis & rheumatology, 0303 health sciences, business.industry, Disease Management, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Antirheumatic Agents, [SDV.IMM]Life Sciences [q-bio]/Immunology, Club, business, Rheumatism
Abstract: International audience
Published: 2019

5. Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer

Author: J Jezequel, Mélanie Cariou, Bogdan Badic, Michel Robaszkiewicz, Laura Samaison, Pascale Marcorelles, Tiphaine Kermarrec, Jean-Pierre Bail, Arnaud Uguen, Jean-Baptiste Nousbaum, Laurent Doucet, Philippe Saliou, Franck Cholet, Fanny Barel, Amélie Bourhis, Anaïs Auffret, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Michel, Geneviève
Subjects: Male, 0301 basic medicine, Databases, Factual, Colorectal cancer, High grade tumor, lcsh:Medicine, PT1 Colorectal Cancer, 0302 clinical medicine, Risk Factors, Submucosa, Tissue Distribution, Registries, lcsh:Science, Lymph node, Aged, 80 and over, Multidisciplinary, Colonoscopy, Middle Aged, 3. Good health, medicine.anatomical_structure, Lymphatic Metastasis, Adenocarcinoma, Female, France, Radiology, Colorectal Neoplasms, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Extra nodal, Aged, Neoplasm Staging, Retrospective Studies, business.industry, lcsh:R, Cancer, Endoscopy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, Lymph Nodes, Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.
Published: 2019

6. Use of Auto-Injector for Methotrexate Subcutaneous Self-Injections: High Satisfaction Level and Good Compliance in SELF-I Study, a Randomized, Open-Label, Parallel Group Study

Author: Alain, Saraux, Christophe, Hudry, Elena, Zinovieva, Hélène, Herman-Demars, Stephanie, Werner-Leyval, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut rhumatologique de Paris 8, Département Médical [Paris] (Nordic Pharma SAS), Nordic Pharma SAS [Paris], Nordic Pharma SAS., Self-I Investigators group : Aouadi L, Arif A, Arty-Hue H, Banal F, Banse C, Baron JJ, Basch A, Berton V, Bitar S, Cantagrel A, Cayla P, Combe B, Cornaille-Lafage G, Duplantier D, Dellaroli ME, Ferrazzi V, Flipo RM, Fulpin J, Gardiol JC, Guilyardi C, Hacene A, Hudry C, Jarrige D, Jourdan M, Laillet H, Lamer F, Lassoued S, Lupo-Mattatia G, Marzynski E, Melac-Ducamp S, Monod P, Naim C, Negrier-Chassaing I, Ngasseu P, Plat D, Prothery D, Roch-Bras F, Saraux A, Schaeverbeke T, Sebaa K, Senbel E, Soubrier M, Sourisseau-Diverres G, Soutif D, Straus C, Tauveron P, Timsit MA, Vedere V, Viu P, Werner-Leyval S., Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Medical Department Nordic Pharma, Paris
Subjects: medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Satisfaction, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Rheumatology, Quality of life, Auto-injector, Internal medicine, medicine, Immunology and Allergy, 030212 general & internal medicine, Rheumatoid arthritis, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Syringe, Original Research, 030203 arthritis & rheumatology, Group study, business.industry, medicine.disease, Auto-Injector, 3. Good health, [SDV] Life Sciences [q-bio], Methotrexate, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC925-935, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Compliance, medicine.drug
Abstract: INTRODUCTION:The objective of the study was to compare compliance and acceptability of a new auto-injector (AI) versus syringe for administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA).METHODS:We conducted a randomized, open-label, parallel group study comparing AI to pre-filled syringe (PFS). Adult patients with RA (ACR/EULAR 2010) receiving MTX (orally or by injection) for at least 3 months were allocated to AI or PFS for 6 months and then were allocated to AI for 6 further months. Two co-primary endpoints were defined at M6: percentage of patients with compliance at least 80%; change in functional capacity assessed by Health Assessment Questionnaire (HAQ). Secondary endpoints included quality of life (RaQoL), RA activity (DAS28), and acceptability. Local safety at injection site was assessed at each visit.RESULTS:Two-hundred and sixty-five patients were randomized. The main analysis was conducted on per protocol set (99 AI and 98 PFS). Compliance was 96.2% in AI and 98.9% in PFS. Good complier rates were 89.9% and 94.9%, thus a difference of - 5.0% (- 18.9%; 8.9%). HAQ remained stable in both groups. No difference was found on RaQoL, change in RA activity, and safety profile. Autonomy, acceptability, and patient satisfaction were better with AI, and patients having had the experience of both AI and PFS preferred AI (p, ClinicalTrials.gov identifier, NCT02553018.
Published: 2018

7. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author: Isabel Almeida, Divi Cornec, Torsten Witte, Tania F. Rowley, Tianlu Li, Elena Carnero-Montoro, Mariana Brandão, Antonio Garcia-Gomez, Nancy Azevedo, Esmeralda Neves, Ana Lisa Taylor Tavares, Ana Campar, Jacques-Olivier Pers, Nicolas Hunzelmann, Ellen De Langhe, Ernst R. Dow, Magdolna Deák, Jorge Kageyama, Francisco Javier Garrancho, Gerard Espinosa, Carlo Chizzolini, Laleh Khodadadi, Falk Hiepe, Maria Angeles Aguirre-Zamorano, Marta E. Alarcón-Riquelme, Rosario Lopez-Pedrera, Anne Buttgereit, Ricard Cervera, Javier Rodríguez-Ubreva, Fernanda Genre, Jerome Wojcik, Begoña Ubilla Garcia, Héctor Navarro-Linares, Maria Orietta Borghi, N.T. Baerlecken, Katja Kniesch, Yolanda Jiménez Gómez, Zuzanna Makowska, Martin Kerick, Elena Trombetta, Pierre-Emmanuel Jouve, Lorenzo Beretta, Ricardo Blanco Alonso, Bénédicte Rouvière, Isabel Díaz Quintero, Michael Zauner, Ralf Lesche, Daniel Toro-Domínguez, Manuel Rodriguez Maresca, Attila Balog, Pier Luigi Meroni, Qingyu Cheng, Georg Stummvoll, Johan Frostegård, Javier Martín, Márta Bocskai, Joerg Mueller, Tommaso Schioppo, Chris Chamberlain, Sonja Dulic, László Kovács, Raquel López Mejías, Velia Gerl, Francesc Català-Moll, Robert J. Benschop, Sara Remuzgo, Carolina Artusi, María Teruel, Eduardo Collantes-Estevez, Miguel A. González-Gay, Silvia Thiel, Bernard Lauwerys, Maria Gerosa, Yves Renaudineau, Pedro Carmona-Sáez, Raquel Faria, Rocío Aguilar-Quesada, Sepideh Babaei, Nuria Barbarroja, Maria Hernandez-Fuentes, María Concepción Fernández Roldán, Sambasiva P. Rao, Aurélie De Groof, Montserrat Alvarez, Anne-Lise Maudoux, Sikander Hayat, Guillermo Barturen, Maria Juarez, Damiana Álvarez-Errico, Alfonso Corrales Martínez, Julie Ducreux, Lucas Le Lann, Norberto Ortego, Jacqueline Marovac, Sandrine Jousse-Joulin, Enrique Raya, Laurence Laigle, Concepción Marañón, Esteban Ballestar, Manuel Martínez-Bueno, Barbara Vigone, Rik Lories, Doreen Belz, Gabriella Kádár, Gaia Montanelli, Fátima Farinha, Divya Thiagaran, M.C. Castro-Villegas, Christophe Jamin, Alain Saraux, Carlos Vasconcelos, Emanuele de Rinaldis, Donatienne Wynar, Enrique de Ramón, Antonio López-Berrio, Tania Anjos, Alejandro Escudero-Contreras, Ian White, Valérie Devauchelle-Pensec, Ignasi Rodríguez-Pintó, Nieves Varela, Quentin Simon, Michaela Lehner, Inmaculada Jiménez Moleón, Aleksandra Maria Dufour, Rafaela Ortega-Castro, Marialbert Acosta-Herrera, Mcdonald Fiona Mcdougall, Yiannis Ioannou, Jonathan Cremer, António Marinho, Jordi Martorell-Marugán, Centre for Genomics and Oncological Research (GENYO) Pfizer, University of Granada, Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, Centro de Genomica e Investigacion Oncologica (GENYO), Department of Bioinformatics, Center for Genomics and Oncological Research (GENYO), Granada, Spain, Institute of Parasitology and Biomedicine (IPB - GRANADA), Spanish National Research Council (CSIC), LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), UCB Pharma, Slough SL1 3WE, United Kingdom, Centre for Genomics and Oncological Reearch (GENYO), Andalusian Public Health System Biobank, Granada, Spain, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Universidade do Porto, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Unidade de Imunologia Clínica, Centro Hospitalar do Porto, Portugal, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Karolinska Institutet [Stockholm], Universidad de Cantabria [Santander], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Klinikum Leverkusen Teaching Hospital of the University of Cologne, Hannover Medical School [Hannover] (MHH), Medical University of Vienna, Vienna, Austria, Medical University of Vienna, General Hospital of Vienna, Hospital Reina Sofía, Hospital Regional Universitario de Málaga [Spain], Hospital Universitario San Cecilio, Hospital Universitario Virgen de las Nieves, Università degli Studi di Milano [Milano] (UNIMI), Université Catholique de Louvain = Catholic University of Louvain (UCL), AltraBio [Lyon], Geneva University Hospital (HUG), University of Szeged [Szeged], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sanofi [Cambridge, MA, USA], Sanofi Genzyme, Eli Lilly, Indianapolis, USA, UCB Celltech [Slough, UK], Institut de Recherches Internationales Servier [Suresnes] (IRIS), Quartzbio, Geneva, Instituto de Parasitología y Biomedicina 'López-Neyra', Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Bellvitge Institute for Biomedical Research, Bayer HealthCare, Berlin, Centre for Genomics and Oncological Research Pfizer [Granada, Spain], University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Michel, Geneviève, Universidad de Granada = University of Granada (UGR), Nantes Université (Nantes Univ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universidade do Porto = University of Porto, University of Cologne, Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Università degli Studi di Milano = University of Milan (UNIMI), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: 0301 basic medicine, Adult, Epigenomics, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cross-sectional study, Immunology, Arthritis, Bioinformatics, Scleroderma, Autoimmune Diseases, Transcriptome, Arthritis, Rheumatoid, 03 medical and health sciences, Epigenome, 0302 clinical medicine, Rheumatology, medicine, Immunology and Allergy, Cluster Analysis, Humans, Lupus Erythematosus, Systemic, Undifferentiated Connective Tissue Diseases, Aged, Mixed Connective Tissue Disease, 030203 arthritis & rheumatology, Inflammation, Science & Technology, Lupus erythematosus, Scleroderma, Systemic, business.industry, Gene Expression Profiling, Case-control study, Middle Aged, medicine.disease, Antiphospholipid Syndrome, 3. Good health, Clinical trial, Gene expression profiling, 030104 developmental biology, Cross-Sectional Studies, Sjogren's Syndrome, Case-Control Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interferons, business, Life Sciences & Biomedicine
Abstract: OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:6 pages:1073-1085 ispartof: location:United States status: published
Published: 2021

8. Hyposialylation Must Be Considered to Develop Future Therapies in Autoimmune Diseases

Author: Christophe Jamin, Anne Harduin-Lepers, Marie Pierre Morel, Cristina Bagacean, Anne Bordron, Maryvonne Dueymes, Jacques-Olivier Pers, Pierre Pochard, Université de Lille, CNRS, Lymphocytes B, Autoimmunité et Immunothérapies [LBAI], Centre Hospitalier Régional Universitaire de Brest [CHRU Brest], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Lille, CNRS, INSERM, CHRU Lille, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Michel, Geneviève
Subjects: sialyltransferase, Review, medicine.disease_cause, Autoimmunity, lcsh:Chemistry, 0302 clinical medicine, MESH: Autoimmune Diseases, MESH: Autoantibodies, MESH: Animals, Precision Medicine, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, biology, sialic acid, autoimmune diseases, immunoglobulin, CD22, therapies, General Medicine, 3. Good health, Computer Science Applications, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, medicine.symptom, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Immunophenotyping, Sialyltransferase, Inflammation, MESH: Precision Medicine, MESH: Sialic Acids, Catalysis, Autoimmune Diseases, Immunophenotyping, Inorganic Chemistry, 03 medical and health sciences, Immune system, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, 030304 developmental biology, Autoantibodies, Autoimmune disease, MESH: Humans, Mechanism (biology), business.industry, Organic Chemistry, medicine.disease, lcsh:Biology (General), lcsh:QD1-999, MESH: Protein Processing, Post-Translational, Immunology, biology.protein, Sialic Acids, business, Protein Processing, Post-Translational, 030215 immunology
Abstract: International audience; Autoimmune disease development depends on multiple factors, including genetic and environmental. Abnormalities such as sialylation levels and/or quality have been recently highlighted. The adjunction of sialic acid at the terminal end of glycoproteins and glycolipids is essential for distinguishing between self and non-self-antigens and the control of pro- or anti-inflammatory immune reactions. In autoimmunity, hyposialylation is responsible for chronic inflammation, the anarchic activation of the immune system and organ lesions. A detailed characterization of this mechanism is a key element for improving the understanding of these diseases and the development of innovative therapies. This review focuses on the impact of sialylation in autoimmunity in order to determine future treatments based on the regulation of hyposialylation.
Published: 2021

9. Ultrasonography of the Salivary Gland in Primary Sjögren Syndrome: Usefulness to Phenotype the Patients

Author: Valérie Devauchelle-Pensec, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Disease, Salivary Glands, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Rheumatology, Major Salivary Gland, Internal medicine, Humans, Immunology and Allergy, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Ultrasonography, 030203 arthritis & rheumatology, Salivary gland, business.industry, medicine.disease, Phenotype, Dermatology, 3. Good health, Lymphoma, stomatognathic diseases, Sjogren's Syndrome, medicine.anatomical_structure, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Rheumatism
Abstract: Major salivary gland ultrasonography (SGUS) is widely used to diagnose primary Sjogren syndrome (pSS) in a large majority of individuals as well as in specific situations, such as when lymphoma is suspected1,2,3. It is a powerful and noninvasive procedure that provides a global image of the parenchymal lesions of the major salivary gland and clearly reflects the effect of the disease on the target tissue4. Some different scoring systems exist, all of which are based on parenchymal inhomogeneity of the parotid and submandibular glands. In this issue of The Journal of Rheumatology , Mossel, et al included consecutive primary Sjogren syndrome (pSS) outpatients in a registry of patients called the RESULT cohort; they described a phenotype associated with an elevated US parenchymal score5. Based on the Hocevar scoring system, an elevated US score was associated with more severe disease, higher European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index (ESSDAI) score, higher levels of IgG and … Address correspondence to Dr. V. Devauchelle-Pensec, Service de rhumatologie, CHRU Cavale Blanche, Boulevard Tanguy Prigent, 29200, Brest, France. Email: valerie.devauchelle-pensec{at}chu-brest.fr.
Published: 2021

10. An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity

Author: Esteban Ballestar, Olivia Castelli, Francesc Català-Moll, Javier Martín, Guillermo Barturen, Marta E. Alarcón-Riquelme, Miguel Barroso, Jacques-Olivier Pers, María Teruel, Zuzanna Makowska, Manuel Martínez-Bueno, Elena Carnero-Montoro, Concepción Marañón, Anne Buttgereit, Martin Kerick, Elena Povedano, Centro de Genomica e Investigacion Oncologica (GENYO), Instituto de Parasitología y Biomedicina 'López Neyra', CSIC, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), 08916 Badalona, Barcelona, Spain, Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Genomics and Oncological Reearch (GENYO), Instituto de Parasitología y Biomedicina López-Neyra (IPBLN-CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Karolinska University Hospital Solna and Karolinska Institutet, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 030203 arthritis & rheumatology, Regulation of gene expression, Genetics, 0303 health sciences, education.field_of_study, [SDV.IMM] Life Sciences [q-bio]/Immunology, Population, Biology, Genetic architecture, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Gene expression, DNA methylation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Epigenetics, education, Gene, 030304 developmental biology, Extracellular matrix organization
Abstract: Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study we identified vast coordinated hypomethylation and overexpression effects, that also exhibit increased variability, in many already known IFN-regulated genes. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of novel genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified new genetic variants associated with SS that mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, DNA methylation, gene expression and SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.
Published: 2021

11. Rheumatological features of Whipple disease

Author: Alice Tison, Pauline Preuss, Clémentine Leleu, François Robin, Adrien Le Pluart, Justine Vix, Guillaume Le Mélédo, Philippe Goupille, Elisabeth Gervais, Grégoire Cormier, Jean-David Albert, Aleth Perdriger, Béatrice Bouvard, Jean-Marie Berthelot, Nathan Foulquier, Alain Saraux, the network of rheumatologists from the Grand Ouest 'VICTOR HUGO', Michel, Geneviève, Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de rhumatologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier La Roche-Sur-Yon, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), This study is part of the French network of University Hospitals VICTOR HUGO (InnoVation en reCherche OsTeo-aRticulaire des Hôpitaux Universitaires du Grand Ouest’)'., Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), 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 de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Systemic disease, medicine.medical_specialty, Saliva, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, Science, Antibiotics, Periodic acid–Schiff stain, Pathogenesis, Gastroenterology, Article, law.invention, Tropheryma whipplei, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, law, Internal medicine, medicine, Signs and symptoms, Polymerase chain reaction, 030203 arthritis & rheumatology, Multidisciplinary, biology, business.industry, Whipple Disease, medicine.disease, biology.organism_classification, 3. Good health, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, business
Abstract: Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. We conducted a retrospective multicentre national study from January 2010 to April 2020 to better characterize the rheumatological features of WD. Classic WD (CWD) was defined by positive periodic acid-Schiff (PAS) staining of a small-bowel biopsy sample, and non-CWD (NCWD) was defined by negative PAS staining of a small-bowel biopsy sample but at least one positive Tropheryma whipplei (TW) polymerase chain reaction (PCR) for a digestive or extradigestive specimen. Sixty-eight patients were enrolled, including 11 CWD patients. Twenty patients (30%) received TNF inhibitors during the WD course, with inefficacy or symptom worsening. More digestive symptoms and systemic biological features were observed in CWD patients than in NCWD patients, but both patient groups had similar outcomes, especially concerning the response to antibiotics and relapse rate. Stool and saliva TW PCR sensitivity were both 100% for CWD and 75% for NCWD and 89% and 60% for small-bowel biopsy sample PCR, respectively. WD encountered in rheumatology units has many presentations, which might result from different pathophysiologies that are dependent on host immunity. Given the heterogeneous presentations and the presence of chronic carriage, multiple TW PCR tests on samples from specific rheumatological sites when possible should be performed, but samples from nonspecific digestive and extradigestive sites also have great value.
Published: 2021

12. Inflammatory Markers are Quickly Improved by Tocilizumab in Early Polymyalgia Rheumatica and Might Predict Early Response to Interleukin-6 Blockade

Author: Valérie Devauchelle-Pensec, Divi Cornec, Alain Saraux, Yves Renaudineau, Guillermo Carvajal Alegria, Michel, Geneviève, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire d'Immunologie et Immunothérapie [Brest], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: musculoskeletal diseases, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, education, Inflammation, Gastroenterology, Polymyalgia rheumatica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, immune system diseases, Internal medicine, medicine, Immunology and Allergy, 10. No inequality, Interleukin 6, skin and connective tissue diseases, health care economics and organizations, Original Research, 030304 developmental biology, Γ-globulins, 030203 arthritis & rheumatology, Autoimmune disease, 0303 health sciences, biology, business.industry, Interleukin-6, Autoantibody, Acute-phase protein, medicine.disease, Acute phase reactants, 3. Good health, chemistry, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business
Abstract: Introduction It is unclear whether polymyalgia rheumatica (PMR) should be considered an inflammatory disease or an autoimmune disease. Methods Eighteen untreated early PMR patients and 18 sex- and age-matched healthy controls (HCs) were included. PMR patients received tocilizumab from week 0 to week 12 and glucocorticoids from week 12 to week 24. Leukocytes, neutrophils, platelets, hemoglobin, γ-globulins, IgG, IgA, and IgM were compared between the PMR patients and HCs and before and after tocilizumab treatment in the PMR group. Results The mean age was 68 ± 7 and 66 ± 11 years, and the mean serum C-reactive protein level was 82 ± 16 and 5 ± 2 mg/l for PMR patients and HCs, respectively. At inclusion, leukocytes (p
Published: 2021

13. Salivary Glands and Periodontal Changes in a Population of Sjögren's and Sicca Syndrome Treated by Pilocarpine: A Pilot Study

Author: Valérie Devauchelle-Pensec, Sylvie Boisramé, Divi Cornec, Alain Saraux, Dewi Guellec, Sandrine Jousse-Joulin, Luc Bressollette, Thierry Marhadour, Jacques-Olivier Pers, Thibaud Depinoy, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Bretagne Occidentale - UFR Odontologie (UBO UFR Odontologie), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Ultrasound Unit Department, Brest, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Population, Salivary glands, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, stomatognathic system, Oral administration, Major Salivary Gland, Internal medicine, Sicca syndrome, medicine, Immunology and Allergy, education, Original Research, Ultrasonography, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Ultrasound, Pilocarpine, 030206 dentistry, Periodontium, 3. Good health, stomatognathic diseases, Sjögren’s syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, medicine.drug
Abstract: Introduction Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown. Methods Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). Vascularization of SG was measured using resistive index (RI) before and after stimulation by lemon juice. Echostructure (measure of glandular length in cm2, evaluation of parotid and submandibular glands parenchymal abnormalities) was assessed at baseline (M0) and after 3 months (M3) of treatment with pilocarpine. A dental consultation was performed at M0 and M3 to evaluate changes in unstimulated salivary flow (USSF), stimulated salivary flow (SSF), and periodontal parameters such as modified gingival index (Lobene), plaque index (Silness), bleeding index, pocket depth, and pH. Results Nineteen patients were included but only 11 received pilocarpine treatment for 3 months, as six stopped pilocarpine due to side effects and two were excluded for other causes. Among the 11 patients who completed the 3-month follow-up, five had primary Sjögren’s syndrome according to the American-European’s classification criteria. As expected, statistical differences were found concerning SSF (p = 0.018) and USSF (p = 0.027) between M0 and M3 while no statistical change in both SG echostructure and vascularization or periodontal evaluation was shown. Conclusions Pilocarpine improved SSF and USSF measurements in sicca syndrome but no ultrasonography of major salivary glands (SGUS) structural and vascular changes were detected as well as periodontal evaluation. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-020-00263-y.
Published: 2020

14. SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients

Author: Brito-Zerón, Pilar, Melchor, Sheila, Seror, Raphaèle, Priori, Roberta, Solans, Roser, Kostov, Belchin, Baldini, Chiara, Carubbi, Francesco, Callejas, Jose Luis, Guisado-Vasco, Pablo, Hernández-Molina, Gabriela, Pasoto, Sandra G, Valim, Valeria, Sisó-Almirall, Antoni, Mariette, Xavier, Carreira, Patricia, Ramos-Casals, Manuel, Brito-Zerón, P, Morcillo, C, Flores-Chávez, A, Ramos-Casals, M, Acar-Denizli, N, Horvath, I F, Szanto, A, Tarr, T, Seror, R, Mariette, X, Mandl, T, Olsson, P, Li, X, Xu, B, Baldini, C, Bombardieri, S, Gottenberg, J E, Gandolfo, S, De Vita, S, Priori, R, Giardina, F, Hernandez-Molina, G, Sánchez-Guerrero, J, Kruize, A A, Hinrichs, A, Valim, V, Isenberg, D, Solans, R, Rischmueller, M, Downie-Doyle, S, Kwok, S-K, Park, S-H, Nordmark, G, Suzuki, Y, Kawano, M, Giacomelli, R, Devauchelle-Pensec, V, Saraux, A, Hofauer, B, Knopf, A, Bootsma, H, Vissink, A, Morel, J, Vollenveider, C, Atzeni, F, Retamozo, S, Moça Trevisano, V, Armagan, B, Kilic, L, Kalyoncu, U, Pasoto, S G, Kostov, B, Sisó-Almirall, A, Consani-Fernández, S, Carubbi, F, Callejas, J L, López-Dupla, M, Pérez-Alvarez, R, Akasbi, M, Guisado-Vasco, P, Sánchez, I, Hospital Universitario 12 de Octubre [Madrid], EULAR standing committee of People with Arthritis/Rheumatism in Europe (PARE), H. CIMA-Sanitas, Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Universidad de Colima [Mexico], Hospital Clinic [Barcelona, Spain], İstanbul Üniversitesi, İstanbul, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, MTA-Debreceni Egyetem, 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, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Skåne University Hospital [Malmö, Suède], Stockholm University, Wuhan University [China], Pisa University Hospital, Nuclear Medicine Unit, Humanitas Gavazzeni, Bergamo, Italy, University Hospitals, Strasbourg, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Federal University of Espírito Santo, University Hospital Vall d’Hebròn [Barcelona, Spain], Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigaciones Biomèdiques August Pi i Sunye (IDIBAPS), Università degli studi di Palermo - University of Palermo, Hospitales Universitarios de Granada/Universidad de Granada, Hospital Universitario Quironsalud, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Rheumatology Unit, Department of Internal Medicine, University of Palermo, Palermo, Italy, and Michel, Geneviève
Subjects: Male, medicine.medical_specialty, Multivariate analysis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Comorbidity, Laboratory abnormality, comorbidities, outcomes, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, Internal medicine, medicine, Humans, In patient, Pharmacology (medical), 030212 general & internal medicine, Registries, Risk factor, Primary Sjögren Syndrome, AcademicSubjects/MED00360, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, Primary SS, SARS-Cov-2, Middle Aged, medicine.disease, 3. Good health, Hospitalization, Sjogren's Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Female, business
Abstract: Objective To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. Methods We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. Results A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. Conclusion Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.
Published: 2020

15. Seasonal effect on fatigue, pain and dryness in primary Sjögren’s syndrome

Author: Jean Sibilia, Pierre-Marie Duret, Raphaèle Seror, Véronique Le-Guern, Xavier Mariette, Jacques-Eric Gottenberg, Nicolas Meyer, Vianney Guardiolle, Aleth Perdriger, Valérie Devauchelle-Pensec, Claire Larroche, Alain Saraux, Service de rhumatologie (Hôpitaux Civils de Colmar), Groupe Méthodes en Recherche Clinique [Strasbourg] (GMRC), Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, 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 médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CNRS, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: MESH: Fatigue, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, [SDV.IMM] Life Sciences [q-bio]/Immunology, Epidemiology, Autoimmune diseases, Pain, Seasons and rheumatic diseases, Primary Sjögren’s syndrome, Outcome measures, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Clinical trials, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective cohort study, MESH: Cohort Studies, Fatigue, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Hydroxychloroquine, MESH: Dry Eye Syndromes, Seasonality, Rheumatology, Infliximab, eye diseases, stomatognathic diseases, Sjogren's Syndrome, MESH: Sjogren's Syndrome, Patient-reported outcomes (PROs), Tears, Dryness, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Dry Eye Syndromes, Seasons, MESH: Pain, medicine.symptom, lcsh:RC925-935, business, MESH: Seasons, medicine.drug, Research Article
Abstract: Background To assess the presence of a seasonal effect on fatigue, pain and dryness in primary Sjögren’s syndrome (pSS). Methods Data (date; visual analogue scales (VAS) for pain, fatigue and dryness) were extracted from three randomised placebo-controlled trials (RCTs) evaluating infliximab (TRIPSS; n = 103 patients), hydroxychloroquine (JOQUER; n = 120 patients) and rituximab (TEARS; n = 120 patients) and from the 5-year follow-up of the ASSESS prospective cohort (n = 395 patients). Data were analysed at each visit for each patient, according to the day, the month of the year and the season. Linear mixed models were used to take into account the repeated structure of the data and to analyse a potential cyclic effect. Results A total of 744, 584, 848 and 682 pain, fatigue and dryness VASs were collected on 632 subjects in spring, summer, fall and winter, respectively. No significant difference was observed in pain, fatigue and dryness, according to the month of the year or the season (all p values > 0.05). Conclusion In pSS, seasonality does not affect patient-reported outcomes (PROs) on fatigue, pain and dryness.
Published: 2020

16. Ultrasound Ulnar Nerve Measurement in a Healthy Population

Author: Bhushan Borotikar, Hoel Letissier, Alain Saraux, Sandrine Jousse-Joulin, Dominique Le Nen, Guillaume Dardenne, CHRU Brest - Service chirurgie orthopédique et traumatologique (CHU - BREST - Orthopédie ), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de Rhumatologie [CHU de la Cavale-Blanche], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), and Michel, Geneviève
Subjects: musculoskeletal diseases, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Intraclass correlation, Elbow, Ulnar tunnel syndrome, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Immunology and Allergy, Medicine, Cross-sectional area, Ulnar nerve entrapment, Ulnar nerve, Original Research, Ultrasonography, 030222 orthopedics, business.industry, Ultrasound, Correction, musculoskeletal system, medicine.disease, body regions, medicine.anatomical_structure, Orthopedic surgery, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Epicondyle, Nuclear medicine, 030217 neurology & neurosurgery
Abstract: Introduction Ulnar tunnel syndrome at the elbow is a common pathology. The ultrasound cross-sectional area is a well-known metric widely accepted in radiology for the description of nerve entrapment. However, the pathological cut-off value remains challenging. The objectives of this study were to (1) describe the ultrasound cross-sectional area measurement of the ulnar nerve at three locations, and (2) to evaluate the inter-observer reliability by two independent ultrasonographers. Methods One-hundred ulnar nerves of 50 asymptomatic individuals were scanned using B-mode and power Doppler ultrasonography. The ultrasound cross-sectional area measurements of the ulnar nerve were performed at three different levels: 2 cm proximal to the epicondyle, at the level of the epicondyle, and 2 cm distal to the epicondyle. Results In our healthy population, we found 21, 24 and 7% of ultrasound cross-sectional area ulnar nerve > 8 mm2, respectively, at three different levels of measurement and 4, 7, and 0% US-CSA ulnar nerve > 10 mm2. The intraclass correlation coefficient measured at three different site levels were good (0.7943, 0.7509) to moderate (0.5701). Conclusions Almost one-quarter of our healthy population had an ultrasound cross-sectional area ulnar nerve more than 8 mm2 and few more than 10 mm2. A cut-off of ultrasound cross-sectional area ulnar nerve measurement more than 10 mm2 could be considered as pathological. No abnormal elbow ulnar nerve vascularization has been seen. This is the first step towards normal B-mode ulnar nerve values at the elbow to further detect pathological US findings as ulnar nerve entrapment.
Published: 2020

17. STIM1 at the plasma membrane as a new target in progressive chronic lymphocytic leukemia

Author: Nelig Le Goux, Marie Potier-Cartereau, Olivier Mignen, Adrian Tempescul, Tinhinane Fali, Sarra Melayah, Yves Renaudineau, Patrice Hemon, Cristina Bagacean, Christophe Vandier, Paul Buscaglia, Marjolaine Debant, Miguel Burgos, Christian Berthou, Jacques-Olivier Pers, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancéropôle Grand-Ouest, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Laboratoire d'Immunologie et Immunothérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: Male, 0301 basic medicine, Cancer Research, ORAI1 Protein, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], chemistry.chemical_compound, Antineoplastic Agents, Immunological, 0302 clinical medicine, hemic and lymphatic diseases, Tumor Cells, Cultured, Immunology and Allergy, Prospective Studies, RNA, Small Interfering, TRPC, B-Lymphocytes, Constitutive Ca2+ entry, Voltage-dependent calcium channel, Chemistry, breakpoint cluster region, Antibodies, Monoclonal, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasm Proteins, [SDV] Life Sciences [q-bio], Treatment Outcome, medicine.anatomical_structure, Oncology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Disease Progression, Molecular Medicine, Female, Signal transduction, Research Article, Thapsigargin, Cell Survival, STIM1, Primary Cell Culture, Immunology, B-cell receptor, lcsh:RC254-282, 03 medical and health sciences, medicine, Humans, Calcium Signaling, Stromal Interaction Molecule 1, Disease outcome, B cell, Aged, TRPC Cation Channels, Pharmacology, Cell Membrane, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 030104 developmental biology, Cancer research, Calcium, CLL
Abstract: Background Dysregulation in calcium (Ca2+) signaling is a hallmark of chronic lymphocytic leukemia (CLL). While the role of the B cell receptor (BCR) Ca2+ pathway has been associated with disease progression, the importance of the newly described constitutive Ca2+ entry (CE) pathway is less clear. In addition, we hypothesized that these differences reflect modifications of the CE pathway and Ca2+ actors such as Orai1, transient receptor potential canonical (TRPC) 1, and stromal interaction molecule 1 (STIM1), the latter being the focus of this study. Methods An extensive analysis of the Ca2+ entry (CE) pathway in CLL B cells was performed including constitutive Ca2+ entry, basal Ca2+ levels, and store operated Ca2+ entry (SOCE) activated following B cell receptor engagement or using Thapsigargin. The molecular characterization of the calcium channels Orai1 and TRPC1 and to their partner STIM1 was performed by flow cytometry and/or Western blotting. Specific siRNAs for Orai1, TRPC1 and STIM1 plus the Orai1 channel blocker Synta66 were used. CLL B cell viability was tested in the presence of an anti-STIM1 monoclonal antibody (mAb, clone GOK) coupled or not with an anti-CD20 mAb, rituximab. The Cox regression model was used to determine the optimal threshold and to stratify patients. Results Seeking to explore the CE pathway, we found in untreated CLL patients that an abnormal CE pathway was (i) highly associated with the disease outcome; (ii) positively correlated with basal Ca2+ concentrations; (iii) independent from the BCR-PLCγ2-InsP3R (SOCE) Ca2+ signaling pathway; (iv) supported by Orai1 and TRPC1 channels; (v) regulated by the pool of STIM1 located in the plasma membrane (STIM1PM); and (vi) blocked when using a mAb targeting STIM1PM. Next, we further established an association between an elevated expression of STIM1PM and clinical outcome. In addition, combining an anti-STIM1 mAb with rituximab significantly reduced in vitro CLL B cell viability within the high STIM1PM CLL subgroup. Conclusions These data establish the critical role of a newly discovered BCR independent Ca2+ entry in CLL evolution, provide new insights into CLL pathophysiology, and support innovative therapeutic perspectives such as targeting STIM1 located at the plasma membrane. Electronic supplementary material The online version of this article (10.1186/s40425-019-0591-3) contains supplementary material, which is available to authorized users.
Published: 2019

18. JAK Inhibitors and Oxidative Stress Control

Author: Amandine Charras, Pinelopi Arvaniti, Christelle Le Dantec, George N. Dalekos, Kaliopi Zachou, Anne Bordron, Yves Renaudineau, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institue of Internal Medicine and Hepatology Larissa Greece, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], medicine.disease_cause, B7-H1 Antigen, 0302 clinical medicine, Immunology and Allergy, STAT1, Phosphorylation, Original Research, chemistry.chemical_classification, ICAM-1, biology, JAK-STAT signaling pathway, ROS, Intercellular Adhesion Molecule-1, 3. Good health, [SDV] Life Sciences [q-bio], STAT1 Transcription Factor, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Immunologic diseases. Allergy, PD-L1, STAT3 Transcription Factor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, primary sjögren's syndrome, Models, Biological, Cell Line, 03 medical and health sciences, medicine, JAK/STAT pathway, Humans, Janus Kinase Inhibitors, Reactive oxygen species, business.industry, stomatognathic diseases, Oxidative Stress, 030104 developmental biology, chemistry, Gene Expression Regulation, STAT protein, biology.protein, Cancer research, Janus kinase, business, lcsh:RC581-607, Reactive Oxygen Species, Oxidative stress, Biomarkers, 030215 immunology
Abstract: International audience; Primary Sjögren's syndrome (SjS) is a complex autoimmune epithelitis, with few treatment options, but the use of Janus kinase (JAK) inhibitors is promising because suppression of the JAK/signal transducer and activator of transcription (STAT) pathway improves sicca manifestations. Playing a primary and pathogenic role in disease development, the oxidative stress response is upregulated in activated salivary gland epithelial cells (SGECs) from patients with SjS. Therefore, the aim of this study was to investigate whether JAK inhibitors would suppress SGEC activation in response to an oxidative stress. For this purpose, the human salivary gland (HSG) cell line was used, and cells were treated with the reactive oxygen species (ROS) inducer hydrogen peroxide (H2O2) or with interferons (IFN Type I and Type II), used as positive controls, to mimic activated SGECs as observed in SjS patients. Afterward, the levels of the intracellular adhesion molecule-1 (ICAM-1) and the regulatory programmed-death ligand-1 (PD-L1) were measured by real-time PCR and flow cytometry, and the STAT1/3 phosphorylation status was assessed by Western blotting. Using the HSG cell line, our results showed that both ICAM-1 and PD-L1 are induced by ROS through pSTAT3, and that this activation pathway is reversed by the use of JAK inhibitors, AG490 and ruxolitinib, as well as by N-acetylcysteine, which is a direct inhibitor of ROS. These findings open new perspectives regarding the pathogenesis and therapeutic possibilities for SjS.
Published: 2019

19. CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes

Author: Sarra Melayah, Marjolaine Debant, Miguel Burgos, Soizic Garaud, Olivier Mignen, Kaushal Parikh, Pierre Youinou, Maikel P. Peppelenbosch, Damien Luque-Paz, David A. Isenberg, Yves Renaudineau, Jacques-Olivier Pers, Rizgar A. Mageed, Gilles Chiocchia, Taher E. Taher, Christian Berthou, Michel, Geneviève, Clinical Chemistry, Gastroenterology & Hepatology, Other departments, Center of Experimental and Molecular Medicine, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, William Harvey Research Institute, Barts and the London Medical School, Pontifical Catholic University of Rio de Janeiro (PUC), Centre for Experimental and Molecular Medicine, Centre For Experimental and Molecular Medicine, Laboratoire d'Immunologie et Immunothérapie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Physiopathologie et Pharmacologie Clinique de la Douleur (LPPD), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Gastroenterology and Hepatology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), and Centre for Rheumatology - London
Subjects: 0301 basic medicine, MAPK/ERK pathway, Male, Small interfering RNA, [SDV.IMM] Life Sciences [q-bio]/Immunology, MAP Kinase Signaling System, Immunology, Receptors, Antigen, B-Cell, Biology, CD5 Antigens, Models, Biological, 03 medical and health sciences, Downregulation and upregulation, immune system diseases, hemic and lymphatic diseases, Cell Line, Tumor, medicine, Immunology and Allergy, Humans, Phosphorylation, B cell, ComputingMilieux_MISCELLANEOUS, Aged, TRPC Cation Channels, Aged, 80 and over, B-Lymphocytes, breakpoint cluster region, Middle Aged, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Cell biology, Interleukin-10, Up-Regulation, Interleukin 10, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Calcium, Female, CD5, Signal transduction, Transcriptome, Research Article
Abstract: CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia (CLL). Important functional properties are associated with CD5 expression in B cells, including signal transducer and activator of transcription 3 activation, IL-10 production and the promotion of B-lymphocyte survival and transformation. However, the pathway(s) by which CD5 influences the biology of B cells and its dependence on B-cell receptor (BCR) co-signaling remain unknown. In this study, we show that CD5 expression activates a number of important signaling pathways, including Erk1/2, leading to IL-10 production through a novel pathway independent of BCR engagement. This pathway is dependent on extracellular calcium (Ca2+) entry facilitated by upregulation of the transient receptor potential channel 1 (TRPC1) protein. We also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 overexpression. In this subgroup of CLL patients, small inhibitory RNA (siRNA) for CD5 reduces TRPC1 expression. Furthermore, siRNAs for CD5 or for TRPC1 inhibit IL-10 production. These findings provide new insights into the role of CD5 in B-cell biology in health and disease and could pave the way for new treatment strategies for patients with B-CLL.
Published: 2018

20. Can artificial intelligence replace manual search for systematic literarure review on cutaneous manifestations in primary Sjögren’s syndrome?

Author: Laurent Misery, Valérie Devauchelle-Pensec, Alain Saraux, Pascal Redou, Laure Orgeolet, Nathan Foulquier, Jacques-Olivier Pers, Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Morvan - CHRU de Brest (CHU - BREST ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Michel, Geneviève, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Européen de Réalité Virtuelle, Laboratoire d'Informatique des Systèmes Complexes (LISYC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: Vasculitis, PubMed, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Skin Diseases, skin manifestation, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Artificial Intelligence, Computer software, Prevalence, Medicine, Humans, Pharmacology (medical), Cutaneous Vasculitis, ComputingMilieux_MISCELLANEOUS, Natural Language Processing, 030203 arthritis & rheumatology, Skin manifestations, Publishing, business.industry, Pruritus, systematic literature review, Reproducibility of Results, Sharp rise, Annular erythema, [SDV] Life Sciences [q-bio], Systematic review, Sjogren's Syndrome, Cheilitis, Erythema, Sjogren’s syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Artificial intelligence, Sjogren s, Periodicals as Topic, business, Software, Systematic Reviews as Topic
Abstract: Objectives Manual systematic literature reviews are becoming increasingly challenging due to the sharp rise in publications. The primary objective of this literature review was to compare manual and computer software using artificial intelligence retrieval of publications on the cutaneous manifestations of primary SS, but we also evaluated the prevalence of cutaneous manifestations in primary SS. Methods We compared manual searching and searching with the in-house computer software BIbliography BOT (BIBOT) designed for article retrieval and analysis. Both methods were used for a systematic literature review on a complex topic, i.e. the cutaneous manifestations of primary SS. Reproducibility was estimated by computing Cohen’s κ coefficients and was interpreted as follows: slight, 0–0.20; fair, 0.21–0.40; moderate, 0.41–0.60; substantial, 0.61–0.80; and almost perfect, 0.81–1. Results The manual search retrieved 855 articles and BIBOT 1042 articles. In all, 202 articles were then selected by applying exclusion criteria. Among them, 155 were retrieved by both methods, 33 by manual search only, and 14 by BIBOT only. Reliability (κ = 0.84) was almost perfect. Further selection was performed by reading the 202 articles. Cohort sizes and the nature and prevalence of cutaneous manifestations varied across publications. In all, we found 52 cutaneous manifestations reported in primary SS patients. The most described ones were cutaneous vasculitis (561 patients), xerosis (651 patients) and annular erythema (215 patients). Conclusion Among the final selection of 202 articles, 155/202 (77%) were found by the two methods but BIBOT was faster and automatically classified the articles in a chart. Combining the two methods retrieved the largest number of publications.
Published: 2019

21. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Author: Margaret Macro, Andrew Ar Belch, Antoine Tinel, Nathalie Meuleman, Jean Yves Mary, Christian Rose, Paula Rodriguez-Otero, Philippe Moreau, Wenming Chen, Michel Attal, Marie Lorraine Chretien, William Renwick, Kihyun Kim, Meletios A. Dimopoulos, Eileen M Boyle, Xavier Leleu, Michael Sturniolo, Thierry Facon, Heinz Ludwig, Mara Silvia Monzini, Vanessa Houck, Elena Zamagni, Adrian Tempescul, Salomon Manier, Cyrille Hulin, Shien Guo, Mohamad Mohty, Bruno M. Costa, Facon T., Dimopoulos M.A., Meuleman N., Belch A., Mohty M., Chen W.-M., Kim K., Zamagni E., Rodriguez-Otero P., Renwick W., Rose C., Tempescul A., Boyle E., Manier S., Attal M., Moreau P., Macro M., Leleu X., Lorraine Chretien M., Ludwig H., Guo S., Sturniolo M., Tinel A., Silvia Monzini M., Costa B., Houck V., Hulin C., Yves Mary J., CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, National and Kapodistrian University of Athens (NKUA), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Cross Cancer Institute [Edmonton, AB, Canada], Service d'immunologie et hématologies biologiques [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), Capital Medical University, Beijing, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Azienda Ospedaliero-Universitaria, Universidad de Navarra [Pamplona] (UNAV), Western Health The University of Melbourne, Université catholique de Lille (UCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Hôpital Universitaire de Caen, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Wilhelminenspital Vienna, Evidera, Celgene Corporation, Celgene International, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Wilhelminenspital Vienna = Wilhelminen Hospital
Subjects: 0301 basic medicine, Male, Cancer Research, [SDV]Life Sciences [q-bio], Dexamethasone, 0302 clinical medicine, Clinical trials, Multiple myeloma, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Lenalidomide, Melphalan, Aged, 80 and over, Frailty, Hematology, Middle Aged, 3. Good health, Thalidomide, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Haematological diseases, Human, Adult, medicine.medical_specialty, FIRST (MM-020) trial, Frail Elderly, Newly diagnosed, Transplant ineligible, Anesthésiologie, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Adverse effect, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Clinical trial, Cancérologie, 030104 developmental biology, Charlson comorbidity index, Prednisone, business, Hématologie
Abstract: Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS–containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

22. Peripheral-blood b-cell subset disturbances in inflammatory joint diseases induced by Tropheryma whipplei

Author: Jacques-Olivier Pers, M. Herbette, Divi Cornec, Clara Le Guillou, Christophe Jamin, Alain Saraux, Dewi Guellec, Sandrine Jousse-Joulin, Jean-Michel Cauvin, Maëlle Le Goff, Thierry Marhadour, Valérie Devauchelle-Pensec, Yves Renaudineau, Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU de Brest, Département information médicale (CHU - BREST ), Laboratoire d'Immunologie et Immunothérapie [Brest], Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Male, 0301 basic medicine, B Cells, Biopsy, [SDV]Life Sciences [q-bio], Artificial Gene Amplification and Extension, Lymphocyte Activation, Polymerase Chain Reaction, Immunoglobulin D, Gastroenterology, Serology, White Blood Cells, Animal Cells, Medicine and Health Sciences, Lymphocytes, health care economics and organizations, Aged, 80 and over, Multidisciplinary, medicine.diagnostic_test, biology, T Cells, Ceftriaxone, Middle Aged, Flow Cytometry, Anti-Bacterial Agents, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Doxycycline, Medicine, Female, Cellular Types, Whipple Disease, Research Article, Hydroxychloroquine, Adult, Subset Analysis, medicine.medical_specialty, Adolescent, Science, Immune Cells, Inflammatory Diseases, Immunology, 030106 microbiology, Naive B cell, education, B-Lymphocyte Subsets, Tropheryma, Surgical and Invasive Medical Procedures, Research and Analysis Methods, Flow cytometry, Tropheryma whipplei, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, medicine, Humans, Antibody-Producing Cells, Molecular Biology Techniques, Molecular Biology, B cell, Aged, Retrospective Studies, Blood Cells, business.industry, Biology and Life Sciences, Cell Biology, Memory B cells, biology.organism_classification, 030104 developmental biology, ROC Curve, biology.protein, business
Abstract: Objective To look for abnormalities in circulating B-cell subsets in patients with rheumatic symptoms of Whipple’s disease (WD). Method Consecutive patients seen between 2010 and 2016 for suspected inflammatory joint disease were identified retrospectively. Results of standardized immunological and serological tests and of peripheral-blood B-cell and T-cell subset analysis by flow cytometry were collected. Patients with criteria suggesting WD underwent PCR testing for Tropheryma whipplei, and those with diagnosis of WD (cases) were compared to those without diagnosis (controls). We used ROC curve analysis to evaluate the diagnostic value of flow cytometry findings for WD. Results Among 2917 patients seen for suspected inflammatory joint disease, 121 had suspected WD, including 9 (9/121, 7.4%) confirmed WD. Proportions of T cells and NK cells were similar between suspected and confirmed WD, whereas cases had a lower proportion of circulating memory B cells (IgD-CD38low, 18.0%±9.7% vs. 26.0%±14.2%, P = 0.041) and higher ratio of activated B cells over memory B cells (4.4±2.0 vs. 2.9±2.2, P = 0.023). Among peripheral-blood B-cells, the proportion of IgD+CD27- naive B cells was higher (66.2%±18.2% vs. 54.6%±18.4%, P = 0.047) and that of IgD-CD27+ switched memory B cells lower (13.3%±5.7% vs. 21.4%±11.9%, P = 0.023), in cases vs. controls. The criterion with the best diagnostic performance was a proportion of IgD+CD27- naive B cells above 70.5%, which had 73% sensitivity and 80% specificity. Conclusion Our study provides data on peripheral-blood B-cell disturbances that may have implications for the diagnosis and pathogenetic understanding of WD.
Published: 2019

23. 17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia

Author: Yves Renaudineau, Anne Banet, Gilles Paintaud, David Ternant, Nathalie Douet-Guilbert, Boutahar Bendaoud, Adrian Tempescul, Anne Bordron, Cristina Bagacean, Mihnea Zdrenghea, Christian Berthou, Hussam Saad, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Génétique moléculaire et génétique épidémiologique, Laboratoire d'Immunologie et Immunothérapie [Brest], Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Tours
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, Antineoplastic Agents, Immunological, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Immunology and Allergy, Molecular Targeted Therapy, Aged, 80 and over, Anti-CD20 monoclonal antibody, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 17p deletion, Chemotherapy regimen, 3. Good health, Fludarabine, [SDV] Life Sciences [q-bio], Leukemia, 030220 oncology & carcinogenesis, Clearance, Molecular Medicine, Female, Rituximab, Chromosome Deletion, IGHV@, medicine.drug, Adult, Bendamustine, medicine.medical_specialty, Cyclophosphamide, Immunology, Short Report, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, medicine, Humans, Pharmacokinetics, Aged, Neoplasm Staging, Pharmacology, business.industry, Genetic Variation, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 030104 developmental biology, Tumor Suppressor Protein p53, business, Chromosomes, Human, Pair 17
Abstract: International audience; Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)). This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study. Accordingly, 44 CLL patients were included in the study, and among them 9 presented a del(17p). Next, a total of 233 rituximab sera were selected for a pharmacokinetic study and analyzed in a two-compartment model showing important differences when del(17p) CLL patients were compared with non-del(17p) patients treated with rituximab and chemotherapy: (1) clearance of rituximab was faster; (2) central volume of rituximab distribution V1 (peripheral blood) was reduced while peripheral volume V2 (lymphoid organs and tissues) was increased; and (3) the rate of rituximab elimination (Kout) was faster. In contrast, the group with a better prognosis harboring isolated del(13q) presented a slower rate of elimination (Kout). Pharmacokinetic parameters were independent from the other factors tested such as age, sex, chemotherapy regimen (fludarabine/cyclophosphamide versus bendamustine), IGHV mutational status, and FCGR3A 158VF status. In conclusion, this study provides an additional argument to consider that del(17p) is effective not only to control chemoresistance but also monoclonal antibody activity, based on higher rituximab turnover.
Published: 2019

24. Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort

Author: Philippe Dieudé, Bernard Combe, Jacques Morel, Nathalie Rincheval, Alain Saraux, Cédric Lukas, Claire Daien, Gaël Mouterde, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U699, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Michel, Geneviève, Mouterde, Gaël, Hôpital Lapeyronie [Montpellier] (CHU), Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, and Université Paris Diderot - Paris 7 (UPD7)
Subjects: 0301 basic medicine, Male, lcsh:Diseases of the musculoskeletal system, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Arthritis, Logistic regression, Severity of Illness Index, Arthritis, Rheumatoid, 0302 clinical medicine, Early arthritis, ComputingMilieux_MISCELLANEOUS, Univariate analysis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Middle Aged, Rheumatoid factor, Prognosis, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Antirheumatic Agents, Cohort, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Seronegative arthritis, 03 medical and health sciences, Internal medicine, medicine, Humans, Autoantibodies, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, ESPOIR cohort, Odds ratio, medicine.disease, Rheumatology, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Anti-citrullinated protein antibodies (ACPA), lcsh:RC925-935, business, Biomarkers, Follow-Up Studies
Abstract: Objective To describe the disease course of patients with early arthritis without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) for these patients within 3 years. Method Patients included in the multicenter ESPOIR cohort were compared at baseline and 3 years by whether they were negative for RF and ACPA (“seronegative”) or positive for RF and/or ACPA (“seropositive”). Univariate analysis was used to determine the association between baseline variables in seronegative patients and RA classification. Stepwise multiple logistic regression was used to identify predictors of RA classification within 3 years, estimating odds ratios (ORs). Results Among 354 seronegative patients, 224/340 with available data (65.9%) fulfilled RA classification at baseline and 189/233 (81.1%) at 3 years. As compared with seropositive patients, seronegative patients had lower DAS28 (p = 0.002) and lower modified total Sharp score (mTSS; p = 0.026) at baseline; DAS28 remission was similar (p = 0.634), but radiographic progression rate was lower in seronegative patients (p
Published: 2019

25. Pharmacokinetics of Prolonged-Release Once-Daily Formulations of Tacrolimus in De Novo Kidney Transplant Recipients: A Randomized, Parallel-Group, Open-Label, Multicenter Study

Author: Mirco Govoni, Paolo Malvezzi, Valérie Garrigue, Arnaud Del Bello, Yannick Le Meur, Giorgia Ciurlia, Silvia Geraci, Elisabeth Cassuto, Lionel Rostaing, Nassim Kamar, Gianluigi Poli, Gabriele Nicolini, Marie Essig, Christophe Mariat, Giovanni Piotti, Michel, Geneviève, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de néphrologie et transplantation rénale [Nice], Hôpital Pasteur [Nice] (CHU), Kidney and Pancreas Transplantation, Global Clinical Development, CHU Saint-Etienne, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Nephrologie-Transplantation Rénale et Hémodialyse [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Departements of nephrology and organ transplantation [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Néphrologie et Transplantation d'organes, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Département de Diabétologie, Urologie, Néphrologie et Endocrinologie (CHU-Grenoble), CHU Grenoble, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Néphrologie, and Hôpital Lapeyronnie
Subjects: Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Urology, Cmax, Biological Availability, 030230 surgery, 030226 pharmacology & pharmacy, Kidney transplant, Drug Administration Schedule, Tacrolimus, PR Tac, 03 medical and health sciences, 0302 clinical medicine, Therapeutic index, Pharmacokinetics, Prolonged release, medicine, Humans, Pharmacology (medical), Molecular Targeted Therapy, Prospective Studies, De novo kidney transplantation, ComputingMilieux_MISCELLANEOUS, Original Research, business.industry, Envarsus, Advagraf, General Medicine, Middle Aged, Kidney Transplantation, 3. Good health, Bioavailability, LCPT, Treatment Outcome, Multicenter study, Research Design, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Immunosuppressive Agents
Abstract: Introduction Different prolonged-release formulations of tacrolimus are available. To date, the pharmacokinetic (PK) profile of LCP-tacrolimus (LCPT; Envarsus®) has not been compared with PR-Tac (Advagraf®) in de novo kidney transplant recipients. These profiles will guide clinical recommendations for the initiation and dose titration strategies of once-daily tacrolimus formulations. Methods This randomized, parallel-group, open-label, multicenter PK study randomized 75 de novo, adult, white kidney transplant recipients to LCPT 0.17 mg/kg/day (n = 37) or PR-Tac 0.20 mg/kg/day (n = 38) for 4 weeks. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations. Results PK analysis (days 1, 3, 7 and 14) included 68 patients (LCPT, n = 33; PR-Tac, n = 35). Similar proportions of patients were within the pre-defined therapeutic tacrolimus trough blood concentration range, with
Published: 2019

26. Against the dryness—an innovative 3D acini model to test new drugs in primary Sjögren’s syndrome

Author: Guillermo Carvajal Alegria, Divi Cornec, Michel, Geneviève, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Lymphocyte B et Auto-immunité (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: 030203 arthritis & rheumatology, 0303 health sciences, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, business.industry, [SDV]Life Sciences [q-bio], Dermatology, 3. Good health, Test (assessment), [SDV] Life Sciences [q-bio], 03 medical and health sciences, Sjogren's Syndrome, 0302 clinical medicine, Rheumatology, medicine, Humans, Dryness, [SDV.IMM]Life Sciences [q-bio]/Immunology, Pharmacology (medical), Sjogren s, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2019

27. Vitamin K antagonist has a higher impact than heparin in preventing circuit clotting in chronic haemodialysis patients

Author: Pierre-Yves Charles, Yannick Le Meur, Tugdual Tanquerel, Hubert Galinat, Michel, Geneviève, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire d'hématologie (Labo Hémato - BREST), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: vitamin K antagonist, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, medicine.medical_treatment, 030232 urology & nephrology, heparin, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine, Chronic hemodialysis, Dosing, coagulation, AcademicSubjects/MED00340, Dialysis, ComputingMilieux_MISCELLANEOUS, Transplantation, chronic haemodialysis, business.industry, Original Articles, Heparin, Vitamin K antagonist, University hospital, 3. Good health, Coagulation, Nephrology, Anesthesia, [SDV.IMM]Life Sciences [q-bio]/Immunology, Hemodialysis, business, medicine.drug
Abstract: Background In dialysis sessions, some data suggest that decreasing or even avoiding additional anticoagulation by heparin is possible among patients already treated with oral anticoagulation. However, the required dose of heparin may actually depend on the pre-dialysis international normalized ratio (INR), which varies from one session to another. The aim of our study was to determine the respective role of INR and heparin dosing in the risk of circuit clotting during chronic haemodialysis. Methods From early 2012 to July 2016, we analysed the totality of dialysis sessions performed at Brest University Hospital among haemodialysis patients treated by vitamin K antagonists (VKA). We established a prediction of circuit clotting on the basis of a simplified score obtained by combining INR and heparin dosing. Results In total, 7184 dialysis sessions among chronic haemodialysis patients under VKA were identified, including 233 with clotting events. The mean INR without clotting events was 2.5 versus 1.8 with clotting events (P 3.0; P Conclusion. Our study established a predictive model of thrombosis risk of dialysis circuits in patients treated by VKA for a given heparin dose and a given INR. This model shows a marginal contribution of heparin to protect against the risk of thrombosis compared with VKA. Moreover, heparin would not appear to be necessary for patients with an INR >2.2.
Published: 2019

28. High reproducibility is attainable in assessing histoprognostic parameters of pT1 colorectal cancer using routine histopathology slides and immunohistochemistry analyses

Author: Mélanie Cariou, Bogdan Badic, Laurent Doucet, Amélie Bourhis, J Jezequel, Laura Samaison, Anaïs Auffret, Franck Cholet, Pascale Marcorelles, Arnaud Uguen, Fanny Barel, Jean-Pierre Bail, Tiphaine Kermarrec, Michel Robaszkiewicz, Jean-Baptiste Nousbaum, CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Brest - Service hépato-gastro-entérologie (CHU de Brest) (CHU Brest - Service hépato-gastro-entérologie), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Registre des Cancers digestifs du Finistère, Brest, Anatomie et Cytologie Pathologique O'Micro, Quimper, Selarl O'Micro, Service de Chirurgie Générale et Viscérale (CGV - BREST), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), BREST - Hépato-Gastro-Entérologie (BREST - HGE), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Michel, Geneviève, Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphovascular invasion, Early colorectal cancer, [SDV]Life Sciences [q-bio], lymphovascular invasion, Adenocarcinoma, Pathology and Forensic Medicine, 03 medical and health sciences, Cytokeratin, 0302 clinical medicine, Biomarkers, Tumor, Medicine, Humans, Lymph node, Pathological, reproducibility, Aged, Aged, 80 and over, Reproducibility, business.industry, Reproducibility of Results, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], tumour budding, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, immunohistochemistry, Immunohistochemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Histopathology, Female, Radiology, Lymph Nodes, business, Colorectal Neoplasms, Kappa
Abstract: International audience; Assessment of the risk of lymph node invasion and tumour recurrence is critical to determine whether additional surgery is required in patients with endoscopically-removed pT1 colorectal cancer (CRC). A reproducible assessment of this risk of recurrence based on histopathological parameters is crucial for relevant therapeutic decisions. The inter-observer reproducibility of these parameters was the subject of our study. Two pathologists independently analysed 163 endoscopically-removed pT1 CRC recorded in a local digestive cancer registry database (Finistère, France). Using haematoxylin-eosin-saffron (HES) and immunohistochemistry slides, they evaluated several parameters related to the risk of tumour recurrence according to the international pT1 CRC-dedicated guidelines. Based on Kappa and intra-class correlation coefficients, good to very good inter-observer agreement was obtained by analysing vertical and lateral margins, submucosal invasion, tumour differentiation and lymphovascular invasion. The reproducibility of tumour budding quantification was only fair on the basis of HES slides but reached a very good agreement using cytokeratin immunohistochemistry. Dual colour cytokeratin and podoplanin immunohistochemistry also improved inter-observer agreement for the detection of lymphovascular invasion. All patients with loco-regional nodal metastases (7 of 101 who underwent complementary surgery) or distant metastases (3 patients) were diagnosed as having a high risk of recurrence and requiring an additional surgery by the two observers. Our study showed that good to very good inter-observer agreement is achievable in evaluating the pathological parameters of recurrence risk in endoscopically-removed pT1 CRC. In addition to HES slides, the detection of lymphovascular invasion and tumour budding can benefit with more reproducible immunohistochemical analyses.
Published: 2019

29. An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases

Author: Pier Luigi Meroni, Margaux Mazeas, Sepideh Babei, Maria Orietta Borghi, Guillermo Barturen, Zuzanna Makowska, Marta E. Alarcón-Riquelme, Yves Renaudineau, Johan Frostegård, Ralf Lesche, Christelle Le Gaffric, Eléonore Bettacchioli, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Istituto Auxologico Italiano, IRCCS, Laboratory of Immunorheumatology, Milan, Italy., Karolinska Institutet [Stockholm], Centre for Genomics and Oncological Research (GENYO) Pfizer, University of Granada, Bayer Pharma AG [Berlin], Michel, Geneviève, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Universidad de Granada = University of Granada (UGR), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: Research paper, Autoimmune diseases, [SDV]Life Sciences [q-bio], RNP, ribonucleoprotein, RA, rheumatoid arthritis, SLE, systemic lupus erythematosus, AUC, area under the curve, APS, primary antiphospholipid syndrome, 0302 clinical medicine, hemic and lymphatic diseases, Immunology and Allergy, SAD, systemic autoimmune diseases, HC, healthy controls, RF - Rheumatoid factor, ComputingMilieux_MISCELLANEOUS, media_common, 0303 health sciences, CCP, cyclic citrulinated peptide, Free Light Chain, Scl, systemic sclerosis, 3. Good health, CXCL10, C-X-C motif chemokine 10, [SDV] Life Sciences [q-bio], M, male, [SDV.IMM]Life Sciences [q-bio]/Immunology, ROC, Receiver Operating Characteristics, RF, rheumatoid factor, Ab, autoantibody, NK, natural killer, medicine.medical_specialty, λ, lambda, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, PC, phosphorylcholine, FLC, free light chains, Free light chains, 03 medical and health sciences, Political science, TH1, T helper type 1, medicine, media_common.cataloged_instance, IFN, interferon, In patient, European union, Interferon signature, Autoantibodies, 030304 developmental biology, MDA, malondialdehyde, 030203 arthritis & rheumatology, F, female, UCTD, undetermined connective tissue disease, RC581-607, SjS, Sjögren's syndrome, RA - Rheumatoid arthritis, VAS, visual analogical scale, Family medicine, MCTD - Mixed connective tissue disease, TNF-R1, tumor necrosis factor receptor 1, κ, kappa, Immunologic diseases. Allergy, MCTD, mixed connective tissue disease, SD, standard deviation
Abstract: The work described has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115565, the resources for which are composed of a financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies'in-kind contribution. We thank all the members of PRECISESADS Consortium and INSERM U1227 for their effort in the sample recruitment, distribution and assessment of the samples used in this study. We are grateful to Dr Wesley H Brooks (Tampa, USA) for editorial assistance and to Valerie Le Troadec for secretarial assistance., High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/ lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou's score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction., Innovative Medicines Initiative Joint Undertaking 115565, European Commission FP7/2007-2013, European Federation of Pharmaceutical Industries and Associations (EFPIA), Institut National de la Sante et de la Recherche Medicale (Inserm), European Commission U1227
Published: 2021

30. ANCA-associated vasculitis — clinical utility of using ANCA specificity to classify patients

Author: Emilie Cornec-Le Gall, Fernando C. Fervenza, Divi Cornec, Ulrich Specks, Michel, Geneviève, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Mayo Clinic [Rochester], and CHRU - Service de néphrologie, dialyse et transplantation rénale
Subjects: 0301 basic medicine, medicine.medical_specialty, Pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Myeloblastin, Microscopic Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Churg-Strauss Syndrome, urologic and male genital diseases, Sensitivity and Specificity, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Predictive Value of Tests, immune system diseases, Proteinase 3, Epidemiology, Eosinophilic, medicine, Humans, Immunologic Factors, cardiovascular diseases, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Peroxidase, Inflammation, 030203 arthritis & rheumatology, biology, business.industry, Granulomatosis with Polyangiitis, Prognosis, medicine.disease, respiratory tract diseases, 3. Good health, 030104 developmental biology, Myeloperoxidase, Predictive value of tests, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business, Granulomatosis with polyangiitis, Microscopic polyangiitis, Biomarkers
Abstract: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of rare syndromes characterized by necrotizing inflammation of small and medium-sized blood vessels and the presence of ANCAs. Several clinicopathological classification systems exist that aim to define homogeneous groups among patients with AAV, the main syndromes being microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). Two main types of ANCA can be detected in patients with AAV. These ANCAs are defined according to their autoantigen target, namely leukocyte proteinase 3 (PR3) and myeloperoxidase (MPO). Patients with GPA are predominantly PR3-ANCA-positive, whereas those with MPA are predominantly MPO-ANCA-positive, although ANCA specificity overlaps only partially with these clinical syndromes. Accumulating evidence suggests that ANCA specificity could be better than clinical diagnosis for defining homogeneous groups of patients, as PR3-ANCA and MPO-ANCA are associated with different genetic backgrounds and epidemiology. ANCA specificity affects the phenotype of clinical disease, as well as the patient's initial response to remission-inducing therapy, relapse risk and long-term prognosis. Thus, the classification of AAV by ANCA specificity rather than by clinical diagnosis could convey clinically useful information at the time of diagnosis.
Published: 2016

31. Biosimilars of filgrastim in autologous stem cell transplantation: certain differences for myeloma patients only

Author: Christian Berthou, Gaelle Guillerm, Jean-Christophe Ianotto, Pascal Delépine, Chloé Henry, Caroline Buors, Christophe Nicol, Marie-Anne Couturier, Céline Tripogney, Adrian Tempescul, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang Bretagne, EFS, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'hématologie (Labo Hémato - BREST), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Michel, Geneviève, Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Male, Oncology, Drug, Cancer Research, medicine.medical_specialty, Filgrastim, [SDV.IMM] Life Sciences [q-bio]/Immunology, media_common.quotation_subject, Treatment outcome, Neutropenia, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Biosimilar Pharmaceuticals, Internal medicine, Granulocyte Colony-Stimulating Factor, medicine, Humans, ComputingMilieux_MISCELLANEOUS, media_common, Postoperative Care, business.industry, Hematopoietic Stem Cell Transplantation, Biosimilar, Hematology, medicine.disease, Recombinant Proteins, 3. Good health, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Multiple Myeloma, business, 030215 immunology, medicine.drug
Abstract: RhuG-CSF reduces the duration of neutropenia induced by chemotherapies. The most frequent drug used for this indication is filgrastim (initially Neupogen®-AMGEN SA). Filgrastim biosimilars have bee...
Published: 2017

32. Distinct Mechanisms of Alterations in DNA Methylation/Demethylation Leading to Myelodysplastic Syndromes/Acute Myeloid Leukemia and Chronic Lymphocytic Leukemia

Author: Wesley H. Brooks, Jean Christophe Ianotto, Cristina Bagacean, Adrian Tempescul, Mihnea Zdrenghea, Anne Bordron, Yves Renaudineau, Marie-Anne Couturier, Christian Berthou, Gaelle Guillerm, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Immunologie et Immunothérapie [Brest], Department of Chemistry, University of South Florida, Tampa, FL, USA., University of South Florida [Tampa] (USF), Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Laboratoire d'Immunologie et Immunothérapie, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 0303 health sciences, Myeloid, Myelodysplastic syndromes, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Myeloid leukemia, Biology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Leukemia, 0302 clinical medicine, medicine.anatomical_structure, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, DNA methylation, medicine, Cancer research, Epigenetics, CD5, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Myelodysplastic syndromes (MDS) represent malignant myeloid disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased risk of progression to acute myeloid leukemia (AML). AML is a highly heterogeneous disease characterized by the presence of large chromosomal translocations, gene fusions as well as mutations in the genes involved in hematopoietic proliferation and differentiation resulting in the accumulation of poorly differentiated myeloid cells. Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia, and is characterized by the clonal proliferation and accumulation of mature, long-lived CD5+ B cells. Epigenetic dysregulations are present in both myeloid disorders and in CLL, but, in contrast to MDS and AML that present gene fusions (TET1/LCX) and somatic mutations in epigenetic regulators (DNMT3A, TET2, IDH1/2), in CLL, epigenetic modifications are not qualitative but mostly quantitative (DNMT3A, TET2) and associated with disease progression. As a consequence, in MDS, AML and CLL, the focal or global DNA methylation/demethylation process is altered. In conclusion, a better qualitative and quantitative understanding of epigenetic regulators during myeloid/lymphoid differentiation, their localization and the co-recruitment of other proteins at specific DNA target sites, could offer us the possibility to modulate hematopoiesis, restore the initial balance, and control disease progression.
Published: 2018

33. Conventional radiography in juvenile idiopathic arthritis: Joint recommendations from the French societies for rheumatology, radiology and paediatric rheumatology

Author: Elisabeth Solau-Gervais, Linda Rossi-Semerano, Brigitte Bader-Meunier, Chantal Job Deslandre, Catherine Adamsbaum, Pauline Marteau, Cécile Gaujoux-Viala, Tu Anh Tran, Irène Lemelle, Sylvain Breton, Christelle Sordet, Julien Wipff, Pascal Pillet, Anne Lohse, Michel De Bandt, Valérie Devauchelle-Pensec, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Service d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de Hautepierre [Strasbourg], CHU de Bordeaux Pellegrin [Bordeaux], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Michel, Geneviève, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Male, musculoskeletal diseases, medicine.medical_specialty, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], education, Arthritis, Recommendations, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, 030212 general & internal medicine, Child, skin and connective tissue diseases, Neuroradiology, Conventional radiography, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, Interventional radiology, General Medicine, Juvenile idiopathic arthritis, medicine.disease, Arthritis, Juvenile, Rheumatology, 3. Good health, [SDV] Life Sciences [q-bio], Radiography, Systematic review, Musculoskeletal, Female, Radiology, business, Structural damage, Erosions, Paediatric rheumatology
Abstract: Background Juvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant. Objective To provide pragmatic guidelines on CR in each non-systemic JIA subtype. Methods A multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee. Results 74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA. Conclusion These first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA. Key Points • CR is a valuable imaging technique in selected indications. • CR is routinely recommended for peripheral joints, when damage risk is high. • CR is recommended according to the damage risk, depending on JIA subtype. • CR is not the first-line technique for imaging of the axial skeleton. Electronic supplementary material The online version of this article (10.1007/s00330-018-5304-7) contains supplementary material, which is available to authorized users.
Published: 2018

34. Time-course of ultrasound abnormalities of major salivary glands in suspected Sjögren's syndrome

Author: Pierre Gazeau, Valérie Devauchelle-Pensec, Divi Cornec, Dewi Guellec, Sandrine Jousse-Joulin, Alain Saraux, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Michel, Geneviève
Subjects: musculoskeletal diseases, Change over time, Adult, Male, medicine.medical_specialty, Pathology, Time Factors, [SDV]Life Sciences [q-bio], Submandibular Gland, Salivary glands, Severity of Illness Index, Statistics, Nonparametric, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, stomatognathic system, Internal medicine, Major Salivary Gland, medicine, Humans, Parotid Gland, 030212 general & internal medicine, Parotid, Monitoring, Physiologic, Retrospective Studies, Ultrasonography, 030203 arthritis & rheumatology, Natural course, Time course, business.industry, Ultrasound, Ultrasonography, Doppler, Middle Aged, Prognosis, eye diseases, [SDV] Life Sciences [q-bio], stomatognathic diseases, Sjogren's Syndrome, Cohort, Female, Sjögren's syndrome, sense organs, Sjogren s, business
Abstract: To evaluate whether major salivary-gland ultrasonography (SGUS) abnormalities change over time in patients with suspected primary Sjögren's syndrome (pSS) during the natural course of the disease.We studied patients with suspected pSS who were included in the Brittany cohort of suspected pSS and underwent SGUS at least twice, as part of the routine diagnostic workup done at baseline then at least 1 year later as an additional investigation deemed appropriate by the physician. The evaluation criteria were the semi-quantitative SGUS score (0-4) for each parotid and submandibular gland, the highest SGUS score among the four glands, and the sum of SGUS scores for the four glands. These scores were compared in patients with and without pSS according to the workup at baseline, and their changes over time were assessed.Of 49 included patients, 29 received a diagnosis of pSS at baseline; none of the remaining 20 patients was diagnosed with pSS at either evaluation. The mean (SD) sum of SGUS scores at baseline was 8.9 (5.6) in patients with and 2.1 (2.9) in those without pSS (P0.01). Mean time between SGUSs was 1.9 (1.6) years. None of the evaluation criteria changed between the two SGUSs in the overall population, pSS group, or group without pSS. Similar results were found in the subgroup with recent-onset symptoms.SGUS abnormalities assessed using a semi-quantitative score did not change significantly during a follow-up of nearly 2 years after an initial evaluation for suspected pSS.
Published: 2018

35. B cell subset distribution is altered in patients with severe periodontitis

Author: Pierre Pochard, Quentin Simon, Sylvie Boisramé, Julien Demoersman, Camille Framery, Assem Soueidan, Jacques-Olivier Pers, LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Odontologie (CHU - BREST - Odontologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Periodontology, Nantes, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nantes Université (Nantes Univ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Michel, Geneviève, and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE)
Subjects: 0301 basic medicine, Male, B Cells, Physiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Pilot Projects, Severity of Illness Index, White Blood Cells, 0302 clinical medicine, Oral Diseases, Animal Cells, Medicine and Health Sciences, Medicine, lcsh:Science, CD20, Multidisciplinary, medicine.diagnostic_test, biology, Flow Cytometry, 3. Good health, Body Fluids, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Blood, RANKL, Female, Cellular Types, Anatomy, Research Article, Adult, Immune Cells, Inflammatory Diseases, Immunology, Oral Medicine, Plasma Cells, B-Lymphocyte Subsets, Context (language use), Severe periodontitis, Flow cytometry, Autoimmune Diseases, 03 medical and health sciences, Humans, Antibody-Producing Cells, Periodontitis, B cell, Periodontal Diseases, Blood Cells, business.industry, lcsh:R, Biology and Life Sciences, 030206 dentistry, Cell Biology, medicine.disease, Memory B cells, B-1 cell, 030104 developmental biology, biology.protein, lcsh:Q, Clinical Immunology, Clinical Medicine, business
Abstract: International audience; Several studies have recently highlighted the implication of B cells in physiopathogenesis of periodontal disease by showing that a B cell deficiency leads to improved periodontal parameters. However, the detailed profiles of circulating B cell subsets have not yet been investigated in patients with severe periodontitis (SP). We hypothesised that an abnormal distribution of B cell subsets could be detected in the blood of patients with severe periodontal lesions, as already reported for patients with chronic inflammatory diseases as systemic autoimmune diseases. Fifteen subjects with SP and 13 subjects without periodontitis, according to the definition proposed by the CDC periodontal disease surveillance work group, were enrolled in this pilot observational study. Two flow cytometry panels were designed to analyse the circulating B and B1 cell subset distribution in association with the RANKL expression. A significantly higher percentage of CD27+ memory B cells was observed in patients with SP. Among these CD27+ B cells, the proportion of the switched memory subset was significantly higher. At the same time, human B1 cells, which were previously associated with a regulatory function (CD20+CD69-CD43+CD27+CD11b+), decreased in SP patients. The RANKL expression increased in every B cell subset from the SP patients and was significantly greater in activated B cells than in the subjects without periodontitis. These preliminary results demonstrate the altered distribution of B cells in the context of severe periodontitis. Further investigations with a larger cohort of patients can elucidate if the analysis of the B cell compartment distribution can reflect the periodontal disease activity and be a reliable marker for its prognosis (clinical trial registration number: NCT02833285, B cell functions in periodontitis).
Published: 2018

36. Hospitalisation rates among patients with primary Sjögren’s syndrome: a population-based study, 1995–2016

Author: Carlotta Nannini, Alvise Berti, Divi Cornec, Sara J. Achenbach, Cynthia S. Crowson, Eric L. Matteson, Gabriel Maciel, Luisa Servioli, Michel, Geneviève, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, Mayo Clinic, Office for Autoimmune Diseases, Medical Clinic 1, Montevideo, Office for Autoimmune Diseases, Medical Clinic 1, Department of Rheumatology, Hospital of Prato, San Raffaele Scientific Institute, Milan, Italy, Mayo Clinic [Rochester], Division of Biomedical Statistics and Informatics, Division of Biomedical Statistics anInformatics, Mayo Clinic School Medicine, Division of Epidemiology, Departments of Health Sciences Research, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Population, Rate ratio, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Immunology and Allergy, In patient, 030212 general & internal medicine, education, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, education.field_of_study, Sjögren Syndrome, business.industry, economic evaluations, health services research, 3. Good health, Immunity disorders, Population based study, [SDV] Life Sciences [q-bio], stomatognathic diseases, sjøgren’s syndrome, Cohort, Sjogren s, business, Cohort study
Abstract: Objective To determine rates and primary discharge diagnoses of hospitalisation in a cohort of patients with incident primary Sjogren’s syndrome (pSS) compared with the general population. Methods This was a retrospective population-based cohort study focused on Olmsted County, Minnesota. The pSS cohort consisted of patients with incident pSS in the 1976–2015 period and was compared with a cohort of individuals without pSS matched 3:1 for age, sex and calendar year, randomly selected from the same population. Hospitalisations in 1995–2016 were examined. Discharge diagnoses were categorised using the Clinical Classifications Software for International Classification of Diseases, 9th revision, Clinical Modification. Results A total of 385 hospitalisations occurred in the 160 patients with pSS during 1592 person-years of follow-up. Among 466 comparators, there were 899 hospitalisations during 4660 person-years of follow-up, resulting in a significantly higher rate of hospitalisations in patients with pSS (rate ratio (RR): 1.25, 95% CI: 1.11 to 1.41). Rates of hospitalisation were increased among patients with pSS for endocrine, nutritional and metabolic diseases and immunity disorders (RR 1.82, 95% CI 1.08 to 2.98), diseases of the musculoskeletal system and connective tissue (RR 1.49, 95% CI 1.05 to 2.05) and for injuries and poisoning (RR 1.46, 95% CI 1.01 to 2.06). While not significantly increased overall, hospitalisations for diseases of the circulatory system were significantly increased in patients with pSS aged ≥75 years (RR 1.54, 95% CI 1.11 to 2.11). Conclusions Patients with pSS experienced higher rates of hospitalisation than the general population. Hospitalisations for endocrine/metabolic disorders, diseases of the circulatory system, diseases of the musculoskeletal system and connective tissue disorders, and injuries were more common among patients with pSS than comparators.
Published: 2018

37. DNA demethylation marks in chronic lymphocytic leukemia: it is time to let the cat out of the bag

Author: Christelle Le Dantec, Mihnea Zdrenghea, Yves Renaudineau, Cristina Bagacean, Christian Berthou, Adrian Tempescul, LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Nantes Université (Nantes Univ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Michel, Geneviève
Subjects: 0301 basic medicine, DNA Hydroxymethylation, DNA methylation, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], DNMT, Biology, medicine.disease, Virology, Molecular biology, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, DNA demethylation, Editorial, DNA hydroxymethylation, medicine, chronic lymphocytic leukemia, TET, ComputingMilieux_MISCELLANEOUS, Biotechnology
Abstract: International audience
Published: 2018

38. Mysterious uncoupled clinical symptoms and interferon signature in Sjögren’s syndrome: limitations of current approaches for unravelling complexity?

Author: Divi Cornec, Laurent Chiche, Hôpital Européen [Fondation Ambroise Paré - Marseille], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Michel, Geneviève
Subjects: 030203 arthritis & rheumatology, 0303 health sciences, business.industry, [SDV]Life Sciences [q-bio], MEDLINE, Hydroxychloroquine, Bioinformatics, Signature (logic), [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Interferon, medicine, Pharmacology (medical), Sjogren s, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, medicine.drug
Abstract: International audience
Published: 2019

39. Abatacept efficacy in rheumatoid arthritis is dependent upon baseline blood B-cell levels

Author: Pierre Gazeau, Alain Saraux, Yves Renaudineau, Pierre Pochard, Jacques-Olivier Pers, Valérie Devauchelle-Pensec, Divi Cornec, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, and Michel, Geneviève
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, B-Lymphocyte Subsets, Pilot Projects, Gastroenterology, Abatacept, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Lymphocyte Count, Baseline (configuration management), ComputingMilieux_MISCELLANEOUS, B cell, 030203 arthritis & rheumatology, business.industry, Prognosis, medicine.disease, 3. Good health, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Antirheumatic Agents, Case-Control Studies, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience
Published: 2015

40. Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

Author: Marina I. Arleevskaya, Albina Z. Shafigullina, Yulia V. Filina, Julie Lemerle, Yves Renaudineau, Kazan State Medical University, Kazan Federal University (KFU), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Michel, Geneviève, Kazan State Medical University (KSMU), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, rheumatoid arthritis, medicine.medical_specialty, Exacerbation, [SDV]Life Sciences [q-bio], Immunology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, Rheumatoid factor, viruses, Family history, Original Research, 030203 arthritis & rheumatology, reactive oxygen species, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Autoantibody, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Erythrocyte sedimentation rate, Rheumatoid arthritis, Cohort, women, lcsh:RC581-607, business, infection symptoms
Abstract: International audience; To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.
Published: 2017

41. Calcium Signaling: From Normal B Cell Development to Tolerance Breakdown and Autoimmunity

Author: Patrice Hemon, Nelig Le Goux, Wesley H. Brooks, Marjolaine Debant, Yves Renaudineau, Sreya Mukherjee, Olivier Mignen, Michel, Geneviève, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), European Space Research and Technology Centre (ESTEC), European Space Agency (ESA), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), School of Education Technology [Kolkata, West Bengal], Jadavpur University, Department of Chemistry, University of South Florida, Tampa, FL, USA., and University of South Florida [Tampa] (USF)
Subjects: 0301 basic medicine, TRPC, [SDV.IMM] Life Sciences [q-bio]/Immunology, B-cell receptor, Receptors, Antigen, B-Cell, Context (language use), Autoimmunity, Biology, medicine.disease_cause, Lymphocyte Activation, Autoantigens, Clonal deletion, Autoimmune Diseases, 03 medical and health sciences, Systemic lupus erythematosus, 0302 clinical medicine, Primary Sjӧgren’s syndrome, Calcium pathway, medicine, Immune Tolerance, Immunology and Allergy, Animals, Humans, Calcium Signaling, Clonal Selection, Antigen-Mediated, B cell, Calcium signaling, B cells, B-Lymphocytes, ORAI, Receptor editing, Cell Differentiation, General Medicine, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Immunology, STIM, [SDV.IMM]Life Sciences [q-bio]/Immunology, Signal transduction, Tolerance, 030215 immunology
Abstract: International audience; Maintenance of self-tolerance of auto-reactive lymphocytes is a fundamental mechanism to prevent the onset of autoimmune diseases. Deciphering the mechanisms involved in the deregulations leading to tolerance disruption and autoimmunity is still a major area of interest to identify new therapeutic targets and options. Ca(2+) signaling plays a major role in B cell normal development and is therefore finely tuned by B cell receptor (BCR)-dependent and independent pathways. Developmental changes in the characteristics of BCR-dependent Ca(2+) signals as well as the modulation of basal intracellular concentration ([Ca(2+)]i) contribute strongly to self-tolerance maintaining mechanisms responsible for the physical or functional elimination of autoreactive B cells such as clonal deletion, receptor editing, and anergy. Implication of Ca(2+) signals in B tolerance mechanisms mainly occurs through the specific activation of transcriptional programs depending on the amplitude, shape, and duration of Ca(2+) signals. A large number of studies reported Ca(2+) signaling defects in autoimmune pathology such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjӧgren's syndrome (pSS). However, the precise nature of the molecular events responsible for these deregulations is not fully understood. Moreover, the demonstration of a direct correlation between Ca(2+) signaling defects and tolerance disruption is still lacking. The recent identification of proteins involved in B cell Ca(2+) signals such as ORAI, stromal interaction molecule and transient receptor potential is opening new horizons for understanding Ca(2+) signaling defects observed in autoimmune diseases and for proposing potentially new therapeutic solutions. This review aims to present an overview of the developmental evolution of BCR dependent Ca(2+) signaling and to place this signaling pathway in the context of mechanisms involved in tolerance maintenance and breakdown.
Published: 2017

42. Characteristics of and risk factors for severe neurological deficit in patients with pyogenic vertebral osteomyelitis: A case-control study

Author: Lemaignen, Adrien, Ghout, Idir, Dinh, Aurélien, Gras, Guillaume, Fantin, Bruno, Zarrouk, Virginie, Carlier, Robert, Loret, Jean-Edouard, Denes, Eric, Greder, Alix, Lescure, François-Xavier, Boutoille, David, Tattevin, Pierre, Issartel, Bertrand, Cottier, Jean-Philippe, Bernard, Louis, Bernard, Adrien, Service de Médecine Interne et Maladies Infectieuses [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinic Research Unit Boulogne, University Hospital A Pare, Services des maladies infectieuses [AP-HP Hôpital Raymond Poincaré, Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Laboratoire de Mathématiques de Besançon (UMR 6623) (LMB), Université de Bourgogne (UB)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Dpt médecine interne [CHU Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [AP-HP], Service de Neurochirurgie [CHRU Tours], Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Service des Maladies Infectieuses [CH de Versailles André Mignot], Centre Hospitalier de Versailles André Mignot (CHV), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Department of Infectious Diseases Clinique du Parc Lyon, Clinique Résidence du Parc, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Communications et en Cybernétique de Nantes (IRCCyN), Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Michel, Geneviève, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], Laboratoire de Mathématiques de Besançon, Chercheur indépendant, Hôpital Beaujon, AP-HP Hôpital Raymond Poincaré [Garches], Centre Hospitalier de Versailles (CHV), Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (Polytech Nantes), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches], Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre Hospitalier de Versailles André Mignot, Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Recherche en Communications et en Cybernétique de Nantes ( IRCCyN ), Mines Nantes ( Mines Nantes ) -École Centrale de Nantes ( ECN ) -Ecole Polytechnique de l'Université de Nantes ( Polytech Nantes ), and Université de Nantes ( UN ) -Université de Nantes ( UN ) -PRES Université Nantes Angers Le Mans ( UNAM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, medicine.medical_specialty, Epidural abscess, [SDV.IMM] Life Sciences [q-bio]/Immunology, Observational Study, 03 medical and health sciences, 0302 clinical medicine, neurologic manifestations, Spinal cord compression, Internal medicine, spinal cord compression, medicine, Vertebral osteomyelitis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, risk factors, 030212 general & internal medicine, Retrospective Studies, business.industry, Osteomyelitis, Hazard ratio, vertebral osteomyelitis, Case-control study, Retrospective cohort study, General Medicine, Odds ratio, Middle Aged, Staphylococcal Infections, medicine.disease, 3. Good health, Surgery, Anti-Bacterial Agents, Treatment Outcome, Epidural Abscess, Case-Control Studies, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Spinal Diseases, France, Nervous System Diseases, business, 030217 neurology & neurosurgery, Follow-Up Studies, Research Article
Abstract: Supplemental Digital Content is available in the text, Severe neurological deficit (SND) is a rare but major complication of pyogenic vertebral osteomyelitis (PVO). We aimed to determine the risk factors and the variables associated with clinical improvement for SND during PVO. This case–control study included patients without PVO-associated SND enrolled in a prospective randomized antibiotic duration study, and patients with PVO-associated SND managed in 8 French referral centers. Risk factors for SND were determined by logistic regression. Ninety-seven patients with PVO-associated SND cases, and 297 controls were included. Risk factors for SND were epidural abscess [adjusted odds ratio, aOR 8.9 (3.8–21)], cervical [aOR 8.2 (2.8–24)], and/or thoracic involvement [aOR 14.8 (5.6–39)], Staphylococcus aureus PVO [aOR 2.5 (1.1–5.3)], and C-reactive protein (CRP) >150 mg/L [aOR 4.1 (1.9–9)]. Among the 81 patients with PVO-associated SND who were evaluated at 3 months, 62% had a favorable outcome, defined as a modified Rankin score ≤ 3. No factor was found significantly associated with good outcome, whereas high Charlson index [adjusted Hazard Ratio (aHR) 0.3 (0.1–0.9)], low American Spinal Injury Association (ASIA) impairment scale at diagnosis [aHR 0.4 (0.2–0.9)], and thoracic spinal cord compression [aHR 0.2 (0.08–0.5)] were associated with poor outcome. Duration of antibiotic treatment was not associated with functional outcome. SND is more common in cervical, thoracic, and S. aureus PVO, in the presence of epidural abscess, and when CRP >150 mg/L. Although neurological deterioration occurs in 30% of patients in early follow-up, the functional outcome is quite favorable in most cases after 3 months. The precise impact of optimal surgery and/or corticosteroids therapy must be specified by further studies.
Published: 2017

43. Anti-DNA and Anti-Nucleosome Antibodies: An Update

Author: Wesley H. Brooks, Julie Lemerle, Yves Renaudineau, Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of Chemistry, University of South Florida, Tampa, FL, USA., University of South Florida [Tampa] (USF), and Michel, Geneviève
Subjects: [SDV]Life Sciences [q-bio], Lupus nephritis, Disease, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Medicine, Nucleosome, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, Anti dna, Systemic lupus erythematosus, biology, business.industry, Autoantibody, medicine.disease, Response to treatment, 3. Good health, [SDV] Life Sciences [q-bio], Immunology, biology.protein, Antibody, business
Abstract: Among the large spectrum of autoantibodies (Ab) detected in systemic lupus erythematosus (SLE), anti-dsDNA Ab have been used to diagnose and assess disease activity for more than 60 years. Anti-dsDNA Ab are often associated with anti-nucleosome Ab, and in clinical practice combining both is helpful for diagnosis, prognosis, and as biomarkers to monitor response to treatment, especially when using drugs that target B cells and Ab production. In general, the association of anti-dsDNA Ab plus anti-nucleosome Ab is linked with disease flares and can indicate lupus nephritis. Moreover and since anti-nucleosome Ab have higher sensitivity and specificity than anti-dsDNA Ab, the former is a useful marker in SLE patients negative for anti-dsDNA Ab and in the diagnosis of certain types of drug-induced lupus.
Published: 2017

44. The Incidence of Arterial and Venous Thrombosis in Antineutrophil Cytoplasmic Antibody–associated Vasculitis

Author: Alvise Berti, Eric L. Matteson, Ulrich Specks, Divi Cornec, Cynthia S. Crowson, Mayo Clinic [Rochester], Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, Mayo Clinic, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Immunology and Allergy, In patient, cardiovascular diseases, 030212 general & internal medicine, Anti-neutrophil cytoplasmic antibody, Venous Thrombosis, 030203 arthritis & rheumatology, business.industry, Incidence, Incidence (epidemiology), Arteries, medicine.disease, 3. Good health, Venous thrombosis, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, High incidence, business, Vasculitis
Abstract: To the Editor: We read with interest in The Journal of Rheumatology the article by Kang, et al , “High Incidence of Arterial and Venous Thrombosis in Antineutrophil Cytoplasmic Antibody-associated Vasculitis,”1 which reported a dramatically high incidence of arterial (ATE) and venous thrombosis events (VTE) in a hospital-based cohort of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV). The study generally supports the previously reported increased risk of ATE and VTE in patients affected by AAV2–8, but has a number of inaccuracies and methodological issues that inflate the incidence rates of ATE and VTE. First, the authors compared clinical and laboratory features at baseline between groups defined by events that occurred during the followup (ATE vs no ATE, and VTE vs no VTE, Table 1 and … Address correspondence to Dr. D. Cornec, CHU Brest, Rheumatology, Boulevard Tanguy Prigent, Brest, 29609, France. E-mail: divi.cornec{at}chu-brest.fr
Published: 2019

45. Could abatacept directly target expanded plasmablasts in IgG4-related disease?

Author: Divi Cornec, Jacques-Olivier Pers, Guillermo Carvajal Alegria, Pierre Pochard, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Rhumatologie [CHU de la Cavale-Blanche], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), LabEX IGO Immunothérapie Grand Ouest, and Michel, Geneviève
Subjects: 0301 basic medicine, Systemic disease, Pathology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Plasma Cells, Immunology, Disease, General Biochemistry, Genetics and Molecular Biology, Abatacept, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Fibrosis, parasitic diseases, medicine, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, integumentary system, business.industry, fungi, medicine.disease, Pathophysiology, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Antirheumatic Agents, Immunoglobulin G, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, IgG4-related disease, Pancreas, business, medicine.drug
Abstract: Yamamoto et al 1 recently reported the case of a patient with long-standing and relapsing IgG4-related disease (IgG4-RD), who developed secondary resistance to rituximab treatment but subsequently improved under abatacept infusions. This interesting observation drives important questions, regarding both IgG4-RD pathophysiology and abatacept mechanisms of action. IgG4-RD is a systemic disease of unknown cause, affecting primarily middle-aged men, characterised by swelling of one or several organs (mainly pancreas, salivary and lachrymal glands, lymphadenopathy, retroperitoneal organs) with infiltration of IgG4-positive plasma cells and fibrosis of involved organs, and high serum IgG4 levels in half of the patients.2 ,3 Several diagnostic or classification systems have been proposed.4 ,5 Its pathophysiology is still ill-defined.6 IgG4-secreting plasmablasts are central players in the disease: they are the main infiltrating cells in affected organs, they are expanded in the circulation, are …
Published: 2016

46. Has the time come for biotherapies in giant cell arteritis and polymyalgia rheumatica?

Author: Valérie Devauchelle-Pensec, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, and Michel, Geneviève
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Giant Cell Arteritis, Antibodies, Monoclonal, Humanized, Polymyalgia rheumatica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, Medicine, Humans, Interleukin 6, Glucocorticoids, ComputingMilieux_MISCELLANEOUS, Aged, 030203 arthritis & rheumatology, biology, business.industry, Interleukin-6, medicine.disease, Dermatology, 3. Good health, Biological Therapy, Giant cell arteritis, 030104 developmental biology, chemistry, Polymyalgia Rheumatica, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business
Abstract: International audience
Published: 2016

47. Multi-center harmonization of flow cytometers in the context of the European 'PRECISESADS' project

Author: Esmeralda Neves, Damiana Álvarez-Errico, Katja Kniesch, Marta E. Alarcón-Riquelme, Christophe Jamin, Aleksandra Maria Dufour, Nuria Barbarroja, Velia Gerl, Concepción Marañón, Jacques-Olivier Pers, Elena Trombetta, Tineke Cantaert, Julie Ducreux, Lucas Le Lann, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Chromatin and Disease Group (Cancer Epigenetics and Biology Programme (PEBC)), Laboratorio de Investigaciones Biomedicas, Fundacion IMABIS. Hospital Virgen de la Victoria, Laboratory of Tissue Homeostasis and Disease, Laborory of Tissue homeostasis and Disease, SS/IREC/RUMA Cliniques Universitaires St Luc, Institut d'ethnologie méditerranéenne, européenne et comparative (IDEMEC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Klinik Für Immunologie Und Rheumatologie, Klinik Fü Immunologie Und Rheumatologie, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Fondazione IRCCS Servizio Di Citometria, Centre for Genomics and Oncological Reearch (GENYO), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Michel, Geneviève
Subjects: 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Computer science, Immunology, Context (language use), Harmonization, computer.software_genre, Antibodies, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Surface marker, Immunology and Allergy, Humans, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Flow Cytometry, 3. Good health, Europe, 030104 developmental biology, Flow (mathematics), Calibration, [SDV.IMM]Life Sciences [q-bio]/Immunology, Data mining, computer, Standard operating procedure
Abstract: The innovative medicine initiative project called PRECISESADS will study 2.500 individuals affected by systemic autoimmune diseases (SADs) and controls. Among extensive OMICS approaches, multi-parameter flow cytometry analyses will be performed in eleven different centers. Therefore, the integration of all data in common bioinformatical and biostatistical investigations requires a fine mirroring of all instruments. We describe here the procedure elaborated to achieve this prerequisite. One flow cytometer chosen as reference instrument fixed the mean fluorescence intensities (MFIs) of 8 different fluorochrome-conjugated antibodies (Abs) using VersaComp Ab capture beads. The ten other centers adjusted their own PMT voltages to reach the same MFIs. Subsequently, all centers acquired Rainbow 8-peak beads data on a daily basis to follow the stability of their instrument overtime. One blood sample has been dispatched and concomitantly stained in all centers. Comparison of leukocytes frequencies and cell surface marker MFIs demonstrated the close sensitivity of all flow cytometers, allowing a multicenter analysis. The effective multi-center harmonization enables the constitution of a workable wide flow cytometry database for the identification of specific molecular signatures in individuals with SADs.
Published: 2016

48. Mutations in GANAB, Encoding the Glucosidase IIα Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease

Author: Cécile Vigneau, Binu Porath, Elizabeth K. Dillinger, Saurabh Baheti, Marie C. Hogan, José Ignacio Herrero, Sarah R. Mauritz, Katharina Hopp, Emilie Cornec-Le Gall, Peter C. Harris, Vladimir G. Gainullin, Christina M. Heyer, Vicente E. Torres, Velibor Tasic, Marie Pierre Audrézet, Marie E. Edwards, Terry Watnick, Charles D. Madsen, Arlene B. Chapman, Yannick Le Meur, Frédéric Lavainne, Carly J. Banks, Claude Férec, Jesus M. Banales, Bharathi V. Reddy, Division of Nephrology and Hypertension, Mayo Clinic, Service de néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry and Molecular Biology, University of Southampton, Mayo Clinic [Rochester], University of Chicago, Clínica Universidad de Navarra [Pamplona], Department of Liver and Gastrointestinal Diseases (Biodonista Health Research Institute), Department of Liver and Gastrointestinal Diseases, Department of Pediatric Nephrology, University Children’s Hospital, Division of Nephrology, University of Maryland [Baltimore], Section of Nephrology University of Chicago, CHU Pontchaillou [Rennes], Service de Néphrologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, This study received support from NIDDK grant DK058816, the Mayo PKD Translational Center (DK090728), an American Heart Association postdoctoral fellowship (B.P.), the Mayo Clinic Nephrology Training Grant (T32DK007013 to V.G.G.), an American Society of Nephrology (ASN) Foundation Kidney Research Fellowship (E.C.-L.G.) and Ben J. Lipps Research Fellowship (K.H.), the Mayo Graduate School (E.K.D.), the Zell Family Foundation, and Robert M. and Billie Kelley Pirnie. The CRISP and HALT-PKD studies were supported by NIDDK cooperative agreements (DK056943, DK056956, DK056957, DK056961, DK062410, DK062408, DK062402, DK082230, DK062411, and DK062401), National Center for Research Resources General Clinical Research Centers, and National Center for Advancing Translational Sciences Clinical and Translational Science Awards. The Genkyst cohort was supported by National Plans for Clinical Research, Groupement Interrégional de Recherche Clinique et d’Innovation (GIRCI Grand Ouest), and the French Society of Nephrology., CHRU - Service de néphrologie, dialyse et transplantation rénale, Hospital Donostia. CIBERehd, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Universidade de Aveiro, National Physical Laboratory [Teddington] (NPL), Cancer du rein : bases moléculaires de la tumorogenèse, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Michel, Geneviève, EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 0301 basic medicine, Male, Candidate gene, 030232 urology & nephrology, Fluorescent Antibody Technique, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Polycystic kidney disease, Genetics(clinical), Child, Genetics (clinical), Cells, Cultured, Microscopy, Confocal, Cysts, Polycystic liver disease, Liver Diseases, Middle Aged, Polycystic Kidney, Autosomal Dominant, female genital diseases and pregnancy complications, 3. Good health, Pedigree, Female, Adult, medicine.medical_specialty, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Article, 03 medical and health sciences, SEC63, Internal medicine, medicine, Genetics, Humans, Immunoprecipitation, Amino Acid Sequence, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, PKD1, Sequence Homology, Amino Acid, PRKCSH, Genetic heterogeneity, alpha-Glucosidases, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Transplantation, 030104 developmental biology, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, CRISPR-Cas Systems
Abstract: International audience; Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (∼85% and ∼15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ∼50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit α (GIIα). Because PRKCSH encodes GIIβ, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIα for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIα. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation.
Published: 2016

49. Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data

Author: Alain Saraux, Benjamin Granger, Francis Guillemin, Xavier Le Loët, Bruno Fautrel, Bernard Combe, Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Rhumatologie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Faculté de Médecine [Nancy], Université de Lorraine ( UL ), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Université de Lorraine (UL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Service de Rhumatologie [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), and Michel, Geneviève
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Epidemiology, Immunology, Population, Rheumatoid Arthritis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Early Rheumatoid Arthritis, Internal medicine, Immunology and Allergy, Medicine, Rheumatoid factor, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, 030212 general & internal medicine, education, Leflunomide, 030203 arthritis & rheumatology, education.field_of_study, Receiver operating characteristic, biology, business.industry, C-reactive protein, medicine.disease, 3. Good health, Surgery, Treatment, Rheumatoid arthritis, Cohort, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, medicine.drug
Abstract: International audience; Introduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX).Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year.Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC)
Published: 2016

50. In-depth characterization of CD24(high)CD38(high) transitional human B cells reveals different regulatory profiles

Author: Sophie Hillion, Quentin Simon, Laëtitia Le Pottier, Divi Cornec, Jacques-Olivier Pers, Rizgar A. Mageed, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Rhumatologie [CHU de la Cavale-Blanche], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), William Harvey Research Institute, Barts and the London Medical School, LabEX IGO Immunothérapie Grand Ouest, Service de rhumatologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), and Michel, Geneviève
Subjects: Adult, Graft Rejection, Male, 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, B-cell receptor, HIV Infections, Biology, CD38, medicine.disease_cause, Flow cytometry, Autoimmunity, Arthritis, Rheumatoid, 03 medical and health sciences, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Membrane Glycoproteins, medicine.diagnostic_test, Effector, CD24, Precursor Cells, B-Lymphoid, breakpoint cluster region, CD24 Antigen, Middle Aged, ADP-ribosyl Cyclase 1, Kidney Transplantation, Phenotype, Cell biology, Sjogren's Syndrome, 030104 developmental biology, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female
Abstract: Background CD24 high CD38 high transitional B cells represent cells at a key stage in their developmental pathway. In addition, these B cells have been widely ascribed regulatory functions and involvement in the control of chronic inflammatory diseases. However, the phenotypic and functional overlap between these cells and regulatory B cells remains controversial. Objective In this study we wanted to explore the regulatory properties of CD24 high CD38 high human B cells. Methods We used multicolor flow cytometry in combination with bioinformatics and functional studies to show that CD24 high CD38 high B cells can be distinguished into multiple subsets with different regulatory functions. Results For the first time, the study reveals that human transitional B cells encompass not only transitional type 1 and type 2 B cells, as previously suggested, but also distinct anergic type 3 B cells, as well as IL-10–producing CD27 + transitional B cells. Interestingly, the latter 2 subsets differentially regulate CD4 + T-cell proliferation and polarization toward T H 1 effector cells. Additional analyses reveal that the percentage of type 3 B cells is reduced and the frequency of CD27 + transitional B cells is increased in patients with autoimmune diseases compared with those in matched healthy subjects. Conclusion This study provides evidence for the existence of different transitional B-cell subsets, each displaying unique phenotypic and regulatory functional profiles. Furthermore, the study indicates that altered distribution of transitional B-cell subsets highlights different regulatory defects in patients with different autoimmune diseases.
Published: 2016

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