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36 results on '"Immunopathologie rénale, récepteurs et inflammation"'

1. Recruitment of CXCR3+ T cells into injured tissues in adult IgA vasculitis patients correlates with disease activity

Author: Bruno Martin, Aurélie Sannier, Renato C. Monteiro, Yolande Richard, Evangeline Pillebout, Cédric Aufray, Laureline Berthelot, Agnès Jamin, Alexandra Audemard-Verger, Eric Daugas, Julie Déchanet-Merville, Bruno Lucas, CHU Cochin [AP-HP], Service de rhumatologie, CHU Bordeaux [Bordeaux], Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), U 699, Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Equipe MC3, Modèles Discrets pour les Systèmes Complexes (Laboratoire I3S - MDSC), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), UMR 1599, Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), RF-ELITE : RF-Electronique Imprimée pour les Télécommunications et l'Energie (XLIM-RFEI), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Le Bihan, Sylvie, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Département d'Anatomo-Pathologie [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Alimentation Adaptations Digestives, Nerveuse et Comportementales (ADNC), Institut National de la Recherche Agronomique (INRA)-centre de rennes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), INSERM U25, Hôpital Necker, Paris, France, Centre National de la Recherche Scientifique (CNRS)-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 de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Martin, Bruno, and Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Immunoglobulin A, Pathology, medicine.medical_specialty, Chemokine, [SDV.IMM] Life Sciences [q-bio]/Immunology, T-cell inﬁltrates, medicine.medical_treatment, Immunology, CXCR3, 03 medical and health sciences, IgA vasculitis, 0302 clinical medicine, Immunology and Allergy, Medicine, CXCL10, CXCL13, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, medicine.disease, 3. Good health, 030104 developmental biology, Cytokine, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, biology.protein, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, T-cell infiltrates, Helper T cells, Chemokines, business, Vasculitis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. Methods: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cyto-metry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by im-munohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age-and sex-matched healthy controls.Results: We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria.Conclusion: Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity.
Published: 2019
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2. Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Emmanuelle Vidal-Petiot, Martin Flamant, H. Fessi, Christian Jacquot, Jean-Jacques Boffa, Caroline du Halgouet, Pascal Houillier, Marion Vallet, Sandra Wagner, Gérard Maruani, Renaud de la Faille, François Vrtovsnik, Pierre Ronco, Eric Thervet, Eric Daugas, Marine Livrozet, Laurence Nicolet-Barousse, Marie Metzger, Bénédicte Stengel, Nahid Tabibzadeh, Alexandre Karras, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network [Lyon] (FCRIN INI-CRCT - Coordination Nationale Réseau FORCE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, CHU Tenon [APHP], Service de Néphrologie et Dialyses [CHU Tenon], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Néphrologie et Hémodialyse [CHU HEGP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, F-CRIN, INICRCT network, Paris, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and NephroTest Study Group: Marine Livrozet, Emmanuel Letavernier, Pierre Ronco, Hafedh Fessi, Emmanuelle Vidal-Petiot, Eric Daugas, Caroline du Halgouet, Renaud de La Faille, Gerard Maruani, Marion Vallet, Laurence Nicolet-Barousse, Alexandre Karras, Christian Jacquot
Subjects: Male, urine concentration ability, 030232 urology & nephrology, Urine osmolality, urologic and male genital diseases, tubular damage, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Prospective Studies, prognostic factor, ComputingMilieux_MISCELLANEOUS, Fasting, Middle Aged, Prognosis, female genital diseases and pregnancy complications, 3. Good health, Survival Rate, Nephrology, Disease Progression, Biomarker (medicine), biomarker, Female, France, medicine.symptom, glomerular filtration rate (GFR), Cohort study, Glomerular Filtration Rate, medicine.medical_specialty, Urinary system, CKD progression, Urology, chronic kidney disease (CKD), 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Risk factor, Renal Insufficiency, Chronic, business.industry, Osmolar Concentration, medicine.disease, measured GFR (mGFR), Decreased glomerular filtration rate, end-stage renal disease (ESRD), Albuminuria, GFR decline, business, Biomarkers, Kidney disease
Abstract: International audience; Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).Study design: Prospective longitudinal cohort study.Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.Predictor: Fasting urinary osmolality measured using delta cryoscopy.Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance.Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.Limitations: Fasting was self-reported.Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
Published: 2019
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3. Evaluation of the performances of ‘typical’ imaging abnormalities of axial spondyloarthritis: results of the cross-sectional ILOS-DESIR study

Author: Romain Beaufort, Philippe Goupille, Maxime Dougados, Pascal Richette, Antoine Feydy, Violaine Foltz, Jean-Denis Laredo, Anna Molto, Laure Gossec, Marie-Martine Lefèvre-Colau, Philippe Dieudé, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Sans affiliation, Hôpital Lariboisière-Fernand-Widal [APHP], Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: Diagnostic Imaging, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Radiography, Immunology, Population, Sensitivity and Specificity, Lesion, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Spondyloarthritis, Spondylarthritis, medicine, Back pain, Immunology and Allergy, Humans, 030212 general & internal medicine, Axial spondyloarthritis, education, 030203 arthritis & rheumatology, Sacroiliac joint, education.field_of_study, medicine.diagnostic_test, business.industry, Reproducibility of Results, Magnetic resonance imaging, Magnetic Resonance Imaging, Spine, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Cross-Sectional Studies, Cohort, epidemiology, Female, Radiology, medicine.symptom, business
Abstract: ObjectiveTo evaluate the prevalence and performance as axial Spondyloarthritis (axSpA) diagnostic feature of radiographic and MRI lesions ‘typical’ of axSpA of the sacroiliac joint (SIJ) and spine in a mechanical chronic back pain (CBP) population and in an axSpA cohort.MethodsCross-sectional multicentre study. Patients: (1) recent onset axSpA (DESIR cohort) and (2) mechanical non-axSpA CBP matched for age and gender (ILOS study). Imaging: radiographs and MR scans were performed identically in both groups. All images were centrally read, blinded for diagnosis and for other imaging findings in the same patient. Statistical analysis: prevalence of lesions ‘typical of axSpA’ were compared in both groups. Sensitivity, specificity and positive likelihood ratios (LR+) of each lesion (and combination of lesions) were calculated.ResultsA total of 98 patients with CBP were included, and compared with 100 patients with recent onset axSpA. SIJ lesions were consistently more frequent in the axSpA group (35.0% vs 11.8% pConclusionOur study confirms that ‘typical’ lesions can also be observed in patients with non-axSpA CBP but that SIJ lesions by all modalities remain the most valuable for diagnosis, including structural lesions of the SIJ. This suggests the potential interest of adding MRI SIJ structural lesions in the definition of MRI abnormalities for axSpA classification.
Published: 2019
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4. Extracellular fluid volume is associated with incident end-stage kidney disease and mortality in patients with chronic kidney disease

Author: Anne-Laure Faucon, Martin Flamant, Marie Metzger, Jean-Jacques Boffa, Jean-Philippe Haymann, Pascal Houillier, Eric Thervet, François Vrtovsnik, Bénédicte Stengel, Guillaume Geri, Emmanuelle Vidal-Petiot, Eric Daugas, Nahid Tabibzadeh, Alexandre Karras, Stéphane Roueff, Marie Courbebaisse, Caroline Prot-Bertoye, Jean-Philippe Bertocchio, Gérard Maruani, Pierre Ronco, Hafedh Fessi, Eric Rondeau, Marine Livrozet, Emmanuel Letavernier, Pablo Urena-Torres, Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Service de Réanimation polyvalente, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [APHP], and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, 030232 urology & nephrology, Urology, Water-Electrolyte Imbalance, Renal function, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Extracellular fluid, Medicine, Humans, Prospective Studies, Risk factor, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Aged, Body surface area, business.industry, Incidence, Hazard ratio, Extracellular Fluid, Middle Aged, medicine.disease, Prognosis, Confidence interval, 3. Good health, 030104 developmental biology, Nephrology, Cohort, Disease Progression, Kidney Failure, Chronic, Female, business, Kidney disease, Glomerular Filtration Rate
Abstract: Volume overload has been shown to be an independent risk factor for mortality in patients receiving chronic dialysis, but data in non-dialysis patients are scarce. Therefore we evaluated the prognostic value of extracellular fluid (ECF) volume for chronic kidney disease (CKD) progression and mortality in a prospective hospital-based cohort with CKD stage 1-4 (NephroTest Study). ECF (scaled to body surface area) and the measured glomerular filtration rate (mGFR) were determined using the distribution volume and clearance of 51Cr-EDTA, respectively. Cause-specific Cox and linear mixed-effect regression models were used to analyze the association of ECF with end-stage kidney disease (ESKD) and mortality, and with mGFR decline, respectively. The 1593 patients were mean age 58.8 years, 67% were men, mean mGFR of 43.6 mL/min/1.73m2 and mean ECF 15.1 L/1.73m2. After a median follow-up of 5.3 years, ESKD occurred in 324 patients and 185 patients died before ESKD. In multivariable analysis, ECF was significantly associated with the risk of ESKD (hazard ratio per 1L/1.73m2 increase: 1.14; 95% confidence interval [1.07; 1.21]) and with a faster GFR decline (adjusted mean difference in mGFR slope per 1L/1.73m2 increase -0.14 [-0.23; -0.05] mL/min/year). The relationship of ECF with mortality was non-linear and not significant (per 1L/1.73m2 increase 0.92, [0.73; 1.16]), below 15L/1.73m2, but significant (1.28; [1.14-1.45]) above 15L/1.73m2. Thus, in this large cohort of carefully phenotyped patients with CKD, ECF was an independent risk factor of CKD progression and mortality. Hence, close monitoring and treatment of fluid overload are important for the clinical management of patients with non-dialysis CKD.
Published: 2019
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5. Renal parenchyma impairment characterization in partial unilateral ureteral obstruction in mice with intravoxel incoherent motion-MRI

Author: Ulrich Blank, Michel Peuchmaur, Simon A. Lambert, Miguel Albuquerque, Marianne Alison, Maguelonne Pons, Liza Ali, Benjamin Leporq, Alaa El Ghoneimi, Marie-Laurence Poli Merol, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence Inflamex [Paris] (Faculté de Médecine Xavier Bichat), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (COMUE) (USPC), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), RMN et optique : De la mesure au biomarqueur, Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Chirurgie pédiatrique et urologie [Hôpital Robert Debré - APHP], Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (COMUE) (USPC), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiologie Pédiatrique [AP-HP Hôpital Robert-Debré], Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologie [Hôpital Beaujon - APHP], Hôpital Beaujon [AP-HP], Service de Pathologie [Hôpital Robert Debré - APHP], Sorbonne Paris Cité-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Chirurgie Pédiatrique [Reims] (CHU de Reims - American Memorial Hospital (Hôpital des enfants)), Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Hôpital des enfants) [Reims], Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, and Paris‐Diderot University, French National Research Agency, Investissements d'Avenir programme, Grant/Award Number: ANR‐11‐IDEX‐0005‐02, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, Association des amis de l'American Memorial Hospital Reims France, Section Française d'Urologie Pédiatrique et de l'Adolescent (SFUPA), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Blank, Ulrich, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie pédiatrique (EA_3102), Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-IFR02, Immunopathologie rénale, récepteurs et inflammation, and Hôpital Robert Debré
Subjects: medicine.medical_specialty, kidney, 030232 urology & nephrology, Urology, Renal function, Scintigraphy, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 030218 nuclear medicine & medical imaging, Motion, 03 medical and health sciences, 0302 clinical medicine, hydronephrosis, Fibrosis, partial unilateral ureteral obstruction, Parenchyma, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, Radiology, Nuclear Medicine and imaging, Hydronephrosis, ComputingMilieux_MISCELLANEOUS, Spectroscopy, Intravoxel incoherent motion, intravoxel incoherent motion, Kidney, medicine.diagnostic_test, business.industry, diffusion, medicine.disease, Magnetic Resonance Imaging, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Mice, Inbred C57BL, Perfusion, medicine.anatomical_structure, Molecular Medicine, business, Ureteral Obstruction
Abstract: International audience; Ureteropelvic junction obstruction constitutes a major cause of progressive pediatric renal disease. The biological mechanisms underlying the renal response to obstruction can be investigated using a clinically relevant mouse model of partial unilateral ureteral obstruction (pUUO). Renal function and kidney morphology data can be evaluated using renal ultrasound, scintigraphy and uro-magnetic resonance imaging (uro-MRI), but these methods are poorly linked to histological change and not all are quantitative. Here, we propose to investigate pUUO for the first time using an intravoxel incoherent motion diffusion sequence. The aim of this study was to quantitatively characterize impairment of the kidney parenchyma in the pUUO model. This quantitative MRI method was able to assess the perfusion and microstructure of the kidney without requiring the injection of a contrast agent. The results suggest that a perfusion fraction (f) reduction is associated with a decrease in the volume of the renal parenchyma, which could be related to decreased renal vascularization. The latter may occur before impairment by fibrosis and the findings are in accordance with the literature using the UUO mice model and, more specifically, on pUUO. Further investigation is required before this technique can be made available for the diagnosis and management of children with antenatal hydronephrosis and to select the optimal timing of surgery if required.Copyright © 2017 John Wiley & Sons, Ltd.
Published: 2018
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6. Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation

Author: Sanae Ben, Mkaddem, Amaya, Murua, Héloise, Flament, Dimitri, Titeca-Beauport, Carine, Bounaix, Luca, Danelli, Pierre, Launay, Marc, Benhamou, Ulrich, Blank, Eric, Daugas, Nicolas, Charles, Renato C, Monteiro, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Ben Mkaddem, Sanae
Subjects: Inflammation, Male, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Science, hemic and immune systems, Proto-Oncogene Proteins c-fyn, environment and public health, Mice, Inbred C57BL, Mice, enzymes and coenzymes (carbohydrates), src-Family Kinases, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, embryonic structures, Animals, Homeostasis, Humans, Female, Phosphorylation, biological phenomena, cell phenomena, and immunity, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling. These SHP-1 signatures are relevant in vivo, as Lyn deficiency exacerbates nephritis and arthritis in mice, whereas Fyn deficiency is protective. Similarly, Fyn-activating signature is detected in patients with lupus nephritis, underlining the importance of this Lyn-Fyn balance. These data show how receptors discriminate negative from positive signals that respectively result in homeostatic or inflammatory conditions.Src-family kinases Fyn and Lyn are signaling components downstream of ITAM-bearing antigen receptors. Here the authors show that by phosphorylating SHP-1 at different residues, Lyn and Fyn can have opposing regulatory effects on ITAM receptors.
Published: 2017
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7. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides

Author: Olivier Aumaître, Olivier Lidove, Chahéra Khouatra, Olivier Decaux, Pascal Cohen, P. Gobert, Claire Blanchard-Delaunay, Philippe Ravaud, Pascal Godmer, Xavier Puéchal, Mohamed Hamidou, Hélène Desmurs-Clavel, Pierre-Louis Carron, Elodie Perrodeau, Marize Ducret, Bernard Bonnotte, Thomas Quemeneur, Christian Pagnoux, François Maurier, Benjamin Terrier, Eric Daugas, Luc Mouthon, Nicolas Limal, Loïc Guillevin, A. Karras, 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), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), 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 ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Valenciennes, Santé - STIC, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Immunopathologie rénale, récepteurs et inflammation, Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin ( 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 Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), 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 ), Hospices Civils de Lyon ( HCL ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université Paris Descartes - Paris 5 ( UPD5 ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université de Rennes (UR)-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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, Azathioprine, Kaplan-Meier Estimate, urologic and male genital diseases, Gastroenterology, Severity of Illness Index, 0302 clinical medicine, immune system diseases, Recurrence, Risk Factors, Clinical endpoint, Immunology and Allergy, 030212 general & internal medicine, skin and connective tissue diseases, treatment, Remission Induction, Middle Aged, 3. Good health, Treatment Outcome, Antirheumatic Agents, Rituximab, Female, systemic vasculitis, Granulomatosis with polyangiitis, Microscopic polyangiitis, Vasculitis, Immunosuppressive Agents, medicine.drug, Systemic vasculitis, Adult, medicine.medical_specialty, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, General Biochemistry, Genetics and Molecular Biology, Drug Administration Schedule, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, Humans, cardiovascular diseases, Lymphocyte Count, Glucocorticoids, Anti-neutrophil cytoplasmic antibody, Aged, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, granulomatosis with polyangiitis, Dose-Response Relationship, Drug, business.industry, medicine.disease, respiratory tract diseases, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business
Abstract: International audience; Objective - To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. Methods - The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed. Results - Among the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p
Published: 2017
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8. The IgA1 immune complex–mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

Author: François Vrtovsnik, Laurent Mesnard, Francine Walker, Leona Raskova Kafkova, Ivan C. Moura, Bruce A. Julian, Renato C. Monteiro, Meetu Kaushik Tiwari, Martin Flamant, Niels Olsen Saraiva Camara, Marie Demion, Jan Novak, Emilie Tissandie, Jonathan M. Chemouny, Marc Benhamou, Houda Tamouza, Laureline Berthelot, Etienne Paubelle, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology and Biophysics, Cornell University [New York], Service Hématologie, CH LYON SUD, Pierre benite, Service d'Anatomie et cytologie pathologique, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Department of Microbiology, University of Alabama at Birmingham [ Birmingham] (UAB), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Cornell University, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)
Subjects: Male, MAPK/ERK pathway, Time Factors, Renal glomerulus, Biopsy, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Antigen-Antibody Complex, Cell Communication, 030204 cardiovascular system & hematology, IgA deposition, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Renin-Angiotensin System, 0302 clinical medicine, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Kidney, Mesangial cell, Podocytes, Angiotensin II, TOR Serine-Threonine Kinases, Glomerulonephritis, IgA nephropathy, Middle Aged, 3. Good health, Proteinuria, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Nephrology, Mesangium, Mesangial Cells, Female, Inflammation Mediators, IgA, Adult, MAP Kinase Signaling System, Article, Nephropathy, Young Adult, 03 medical and health sciences, Antigens, CD, Receptors, Transferrin, medicine, Humans, IMUNOLOGIA, Aged, Cell Proliferation, 030304 developmental biology, Interleukin-6, business.industry, Glomerulonephritis, IGA, medicine.disease, Immunoglobulin A, Enzyme Activation, Immunology, Calcium, Cytokine secretion, Phosphatidylinositol 3-Kinase, business, Angiotensin II Type 1 Receptor Blockers, Proto-Oncogene Proteins c-akt
Abstract: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and has significant morbidity and mortality as 20–40% of patients progress to end-stage renal disease (ESRD) within 20 years after disease onset. We aimed to gain insight into the molecular mechanisms involved in IgAN progression. A systematic evaluation of renal biopsy specimens from IgAN patients revealed that the MAPK/ERK signaling pathway was activated in mesangial areas of patients presenting with >1 g/day proteinuria and elevated blood pressure, but was absent in biopsy specimens from IgAN patients with modest proteinuria (
Published: 2012
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9. Identification of NF-κB and PLCL2 as new susceptibility genes and highlights on a potential role of IRF8 through interferon signature modulation in systemic sclerosis

Author: Matthieu Giraud, Erika Salvi, Paola Caramaschi, Nadira Ruzehaji, Cristiane Kayser, Jérôme Avouac, Marco Matucci-Cerinic, Daniele Cusi, Elisabeth Diot, Philippe Dieudé, Yannick Allanore, Eugénie Koumakis, Giovanna Cuomo, Maria Arismendi, Valeria Riccieri, Eric Hachulla, Paolo Airò, Barbara Ruiz, 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), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Département Hospitalo-Universitaire (DHU), Rheumatology and Clinical Immunology, Spedali Civili, Department of Medicine, Surgery, and Dentistry, University of Milano, Genomics and Bioinformatics Platform, Fondazione Filarete, Azienda Ospedaliera Careggi, Largo Giovanni Alessandro Brambilla, Department of Biology and Biotechnology 'Charles Darwin', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service de Médecine Interne, Hôpital Bretonneau, Rheumatology Unit, University of Verona (UNIVR), Division of Rheumatology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Arismendi, Maria, Giraud, Matthieu, Ruzehaji, Nadira, Dieudé, Philippe, Koumakis, Eugenie, Ruiz, Barbara, Airo, Paolo, Cusi, Daniele, Matucci Cerinic, Marco, Salvi, Erika, Cuomo, Giovanna, Hachulla, Eric, Diot, Elisabeth, Caramaschi, Paola, Riccieri, Valeria, Avouac, Jérôme, Kayser, Cristiane, Allanore, Yannick, Bos, Mireille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli studi di Verona = University of Verona (UNIVR), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Institut Cochin (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 Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Roma 'La Sapienza' [Rome], Università degli Studi di Verona, and Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP]
Subjects: Adult, Male, Immunology, Locus (genetics), Genome-wide association study, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Follow-Up Studie, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Primary biliary cirrhosis, Rheumatology, Pleiotropism, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Immunology and Allergy, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allele, skin and connective tissue diseases, Interferon Regulatory Factor, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, 0303 health sciences, Scleroderma, Systemic, business.industry, Intracellular Signaling Peptides and Proteins, Case-control study, NF-kappa B, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Intracellular Signaling Peptides and Protein, Case-Control Studies, Interferon Regulatory Factors, Female, business, Case-Control Studie, Research Article, Follow-Up Studies, Human
Abstract: Introduction Systemic sclerosis (SSc) and primary biliary cirrhosis (PBC) are rare polygenic autoimmune diseases (AIDs) characterized by fibroblast dysfunction. Furthermore, both diseases share some genetic bases with other AIDs, as evidenced by autoimmune gene pleiotropism. The present study was undertaken to investigate whether single-nucleotide polymorphisms (SNPs) identified by a large genome-wide association study (GWAS) in PBC might contribute to SSc susceptibility. Methods Sixteen PBC susceptibility SNPs were genotyped in a total of 1,616 patients with SSc and 3,621 healthy controls from two European populations (France and Italy). Results We observed an association between PLCL2 rs1372072 (odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.12 to 1.33, Padj = 7.22 × 10−5), nuclear factor-kappa-B (NF-κB) rs7665090 (OR = 1.15, 95% CI 1.06 to 1.25, Padj = 0.01), and IRF8 rs11117432 (OR = 0.75, 95% CI 0.67 to 0.86, Padj = 2.49 × 10−4) with SSc susceptibility. Furthermore, phenotype stratification showed an association between rs1372072 and rs11117432 with the limited cutaneous subgroup (lcSSc) (Padj = 4.45 × 10−4 and Padj = 0.001), whereas rs7665090 was associated with the diffuse cutaneous subtype (dcSSc) (Padj = 0.003). Genotype-mRNA expression correlation analysis revealed that the IRF8 protective allele was associated with increased interferon-gamma (IFN-γ) expression (P = 0.03) in patients with SSc but decreased type I IFN (IFIT1) expression in patients and controls (P = 0.02). In addition, we found an epistatic interaction between NF-κB and IRF8 (OR = 0.56, 95% CI 0.00 to 0.74, P = 4 × 10−4) which in turn revealed that the IRF8 protective effect is dependent on the presence of the NF-κB susceptibility allele. Conclusions An analysis of pleiotropic genes identified two new susceptibility genes for SSc (NF-κB and PLCL2) and confirmed the IRF8 locus. Furthermore, the IRF8 variant influenced the IFN signature, and we found an interaction between IRF8 and NF-κB gene variants that might play a role in SSc susceptibility. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0572-y) contains supplementary material, which is available to authorized users.
Published: 2015
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10. Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis

Author: Philippe Dieudé, Arnaud Constantin, Jean Sibilia, Jacques Tebib, Bernard Combe, Xavier Le Loët, Maxime Dougados, Steven Gazal, Pierre-Antoine Juge, Xavier Mariette, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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, Hôpital Bicêtre, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Rouen, Normandie Université (NU), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and univOAK, Archive ouverte
Subjects: rheumatoid arthritis, 0301 basic medicine, gene polymorphism, Immunology, Population, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, medicine, Immunology and Allergy, education, STAT4, pharmacogenetics, 030203 arthritis & rheumatology, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, C-reactive protein, medicine.disease, 030104 developmental biology, Tyrosine kinase 2, Rheumatoid arthritis, biology.protein, IRF7, Rituximab, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, IRF5, medicine.drug
Abstract: Background The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 ( IRF5 and IRF7 ), tyrosine kinase 2 ( TYK2 ), signal transducer and activator of transcription 4 ( STAT4 ) and osteopontin ( SPP1 ). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). Methods Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. Results The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34×10 −6 , OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%. Conclusion Our results support the contribution of the IRF5 , SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24.
Published: 2017
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11. HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia

Author: Michael Dussiot, Carmen Garrido, Yves Beuzard, Samuel Demarest, Geneviève Courtois, Isaure Chauvot de Beauchêne, Stany Chretien, Philippe Leboulch, Olivier Hermine, Zakia Belaid-Choucair, Ivan Moura, Thiago Trovati Maciel, Adonis Hazoumé, Michaela Fontenay, Véronique Baudin-Creuza, Margaux Sevin, Luba Tchertanov, Jean-Antoine Ribeil, Jean-Benoît Arlet, Christian Auclair, Flavia Guillem, Guillaume Marcion, Renaud Seigneuric, Olivier Negre, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Pathologie de la polymérisation des protéines. Substitut du sang et pathologie moléculaire du globule rouge, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Maladies Emergentes et des Thérapies Innovantes ( IMETI ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Thérapie génique et contrôle de l'expansion cellulaire ( UMR E007 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Institut Necker Enfants-Malades ( INEM - UM 111 (UMR 8253 / U1151) ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), and Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) )
Subjects: Ineffective erythropoiesis, Cytoplasm, Erythroblasts, Cell Survival, Mutant, Apoptosis, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, alpha-globin, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, medicine.disease_cause, Protein Refolding, 03 medical and health sciences, 0302 clinical medicine, alpha-Globins, Bone Marrow, hemic and lymphatic diseases, medicine, Humans, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Erythropoiesis, GATA1 Transcription Factor, HSP70 Heat-Shock Proteins, Molecular Targeted Therapy, Cells, Cultured, HSP70, 030304 developmental biology, Regulation of gene expression, Cell Nucleus, 0303 health sciences, Multidisciplinary, Caspase 3, beta-Thalassemia, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], GATA1, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Molecular biology, Hsp70, Enzyme Activation, Kinetics, Gene Expression Regulation, 030220 oncology & carcinogenesis, Chaperone (protein), biology.protein, beta-Thalassaemia, Protein Binding
Abstract: International audience; β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates. Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage. We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of maturation. Although erythroid transcription factor GATA-1, the master transcriptional factor of erythropoiesis, is a caspase-3 target, it is not cleaved during erythroid differentiation. We have shown that, in human erythroblasts, the chaperone heat shock protein70 (HSP70) is constitutively expressed and, at later stages of maturation, translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. The primary role of this ubiquitous chaperone is to participate in the refolding of proteins denatured by cytoplasmic stress, thus preventing their aggregation. Here we show in vitro that during the maturation of human β-TM erythroblasts, HSP70 interacts directly with free α-globin chains. As a consequence, HSP70 is sequestrated in the cytoplasm and GATA-1 is no longer protected, resulting in end-stage maturation arrest and apoptosis. Transduction of a nuclear-targeted HSP70 mutant or a caspase-3-uncleavable GATA-1 mutant restores terminal maturation of β-TM erythroblasts, which may provide a rationale for new targeted therapies of β-TM
Published: 2014
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12. Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

Author: Jacques Morel, Philippe Dieudé, Arnaud Constantin, Adeline Ruyssen-Witrand, Jean Sibilia, B. Jamard, K. Dawidowicz, Anne Cambon-Thomsen, Cédric Lukas, Delphine Nigon, Alain Cantagrel, Service de rhumatologie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de rhumatologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Département de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, 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), Université Paris Diderot - Paris 7 (UPD7), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Subjects: Male, [SDV]Life Sciences [q-bio], MESH: Interleukin-2 Receptor alpha Subunit, Gastroenterology, Arthritis, Rheumatoid, Cohort Studies, Single nucleotid polymorphism, MESH: Genotype, Genotype, MESH: Autoantibodies, MESH: Cohort Studies, education.field_of_study, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Middle Aged, IL-2RB, IL-2RA, MESH: Interleukin-2 Receptor beta Subunit, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Cohort, Female, MESH: Disease Progression, Adult, medicine.medical_specialty, Population, Single-nucleotide polymorphism, Peptides, Cyclic, Polymorphism, Single Nucleotide, Rheumatology, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, education, MESH: Peptides, Cyclic, Autoantibodies, Disease progression, MESH: Humans, business.industry, Haplotype, Interleukin-2 Receptor alpha Subunit, Autoantibody, MESH: Adult, MESH: Haplotypes, medicine.disease, MESH: Male, Interleukin-2 Receptor beta Subunit, Haplotypes, IL2RB, Immunology, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives To assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients. Methods This work is derived from 2 prospective cohorts of early RA: ESPOIR ( n = 439) and RMP ( n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions. Results The AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14–3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68–6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94–18.69], p = 0.002) on the risk of erosions in ACPA+ patients. Conclusion A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.
Published: 2014

13. Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data from the French ESPOIR cohort

Author: Nicaise-Roland , Pascale, Nogueira , Leonor, Demattei , Christophe, De Chaisemartin , Luc, Rincheval , Nathalie, Cornillet , Martin, Grootenboer-Mignot , Sabine, Dieudé , Philippe, Dougados , Maxime, Cantagrel , Alain, Meyer , Olivier, Serre , Guy, Chollet-Martin , Sylvie, Saraux , Alain, Unité différenciation épidermique et auto-immunité rhumatoïde ( UDEAR ), Université Toulouse III - Paul Sabatier ( UPS ), 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 ), Laboratoire de Biostatistique, Epidémiologie, Santé Publique et Informatique Médicale ( BESPIM ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Service Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), 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), Laboratoire de Biostatistique, Epidémiologie, Santé Publique et Informatique Médicale (BESPIM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie Toulouse Purpan (CPTP), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], Arthritis, MESH : Fibrinogen, Autoantigens, MESH : Early Diagnosis, Serology, Arthritis, Rheumatoid, 0302 clinical medicine, MESH: Early Diagnosis, MESH : Peptides, Cyclic, Immunology and Allergy, MESH: Autoantibodies, MESH : Female, skin and connective tissue diseases, Immunoassay, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, Middle Aged, MESH : Immunoassay, Connective tissue disease, 3. Good health, MESH: Autoantigens, Rheumatoid arthritis, Cohort, Female, France, MESH : Sensitivity and Specificity, MESH: Immunoassay, musculoskeletal diseases, medicine.medical_specialty, MESH : Male, Immunology, Peptides, Cyclic, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, MESH : Autoantibodies, medicine, Humans, Vimentin, MESH : Middle Aged, MESH : France, MESH: Peptides, Cyclic, Autoantibodies, 030203 arthritis & rheumatology, MESH : Vimentin, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, Autoantibody, Fibrinogen, MESH : Citrulline, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, MESH: France, Early Diagnosis, MESH : Autoantigens, MESH: Fibrinogen, MESH : Arthritis, Rheumatoid, Citrulline, MESH: Vimentin, business, MESH: Citrulline, MESH: Female, Rheumatism, 030215 immunology
Abstract: International audience; OBJECTIVES: To compare the performance of anticitrullinated peptides/protein antibodies (ACPA) detected by three immunoassays in the French ESPOIR cohort of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) and to study the relationship between ACPA and disease activity. METHODS: A diagnosis of RA (1987 American College of Rheumatology (ACR) criteria) was established at baseline in 497 patients and after a 2-year follow-up in 592 patients. At baseline, antibodies to citrullinated fibrinogen (AhFibA), antimutated citrullinated vimentin (anti-MCV) and anticyclic citrullinated peptide (anti-CCP2) were assayed and the individual and combined diagnostic sensitivities and predictive values of the tests were determined. Relationships between ACPA positivity and the 28-joint disease activity score and Health Assessment Questionnaire scores were analysed. RESULTS: At a diagnostic specificity of at least 98%, the three tests exhibited similar diagnostic sensitivities (47-48.5%). When considering as positive patients with at least one positive test, the sensitivity increased to 53.5% with a probable loss of specificity. Among the patients classified as having UA at baseline, 30% were positive for one ACPA, the positive predictive values for RA of the three tests ranging from 73% to 80% but increasing when two tests were associated. Whatever the test used, the addition of ACPA positivity to the 1987 criteria enhanced their sensitivity by 6%, close to that of the 2010 ACR/European League Against Rheumatism (EULAR) criteria. CONCLUSIONS: In early arthritis, AhFibA, anti-MCV and anti-CCP2 showed similar diagnostic sensitivity with a high diagnostic specificity and a similar high positive predictive value for RA. Adding ACPA to the 1987 ACR criteria significantly increased the number of patients classified as having RA, confirming the validity of the recent inclusion of the serological criterion in the ACR/EULAR criteria.
Published: 2013
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14. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren's syndrome. Data at enrollment in the prospective ASSESS cohort

Author: Jean-Jacques Dubost, Philippe Dieudé, Jacques-Eric Gottenberg, Valérie Devauchelle-Pensec, Joelle Benessiano, Anne-Laure Fauchais, Philippe Ravaud, Jean Sibilia, Vincent Goëb, Xavier Puéchal, Damien Sène, Raphaèle Seror, S. Rist, Olivier Vittecoq, Véronique Le Guern, Pierre Yves Hatron, Gaetane Nocturne, Eric Hachulla, Jacques Morel, Corinne Miceli-Richard, Claire Larroche, Alain Saraux, Aleth Perdriger, Xavier Mariette, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de médecine interne, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Avicenne [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Rhumatologie ( CLERMONT - RHUMATO ), CHU Clermont-Ferrand, Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -CHU Limoges, Service de rhumatologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital avicenne, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre de Référence des microangiopathies thrombotiques ( CNR-MAT ), service d'hématologie-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Lapeyronie [Montpellier] ( CHU ), Service de rhumatologie, Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hôpital Lariboisière, Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], CHU Le Kremlin-Bicêtre ( Rheumatology Department ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Rhumatologie (CLERMONT - RHUMATO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Calvez, Ghislaine
Subjects: Male, Systemic disease, B Cells, Lymphoma, Epidemiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Gastroenterology, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, B-Cell Activating Factor, Pathology, Prospective Studies, Prospective cohort study, lcsh:Science, 0303 health sciences, Multidisciplinary, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Sjogren's Syndrome, Cohort, Medicine, Female, Research Article, medicine.medical_specialty, Sjogren Syndrome, Clinical Research Design, Immune Cells, Immunoglobulins, Autoimmune Diseases, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, Severity of illness, medicine, Humans, B-cell activating factor, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, [ SDV ] Life Sciences [q-bio], business.industry, Beta-2 microglobulin, lcsh:R, medicine.disease, Rheumatology, Biomarker Epidemiology, Immunology, lcsh:Q, Clinical Immunology, Immunoglobulin Light Chains, business, beta 2-Microglobulin, Biomarkers, General Pathology
Abstract: International audience; OBJECTIVES: To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment. METHODS: Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the "Assessment of Systemic Signs and Evolution of Sjögren's Syndrome" (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). RESULTS: Patient median age was 58 (25(th)-75(th): 51-67) and median disease duration was 5 (2-9) years. Median ESSDAI at enrollment was 2 (0-7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]-[11] vs 2 [0-7], P = 0.03; 4 [1]-[11] vs 2 [0-7], P< 0.0001); 4 [2]-[10] vs 2 [0-6.6], P< 0.0001 and 4 [2-8.2] vs 2 [0-7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1-3665.5) vs 898.9 (715.9-1187.2) pg/ml, P = 0.01 and 2.6 (2.2-2.9) vs 2.1 (1.8-2.6) mg/l, P = 0.04, respectively). CONCLUSION: In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.
Published: 2013
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15. Body mass index influences the response to infliximab in ankylosing spondylitis

Author: Florence Tubach, Gilles Hayem, Anaïs Gardette, Sébastien Ottaviani, Olivier Meyer, André Kahan, Elisabeth Palazzo, Philippe Dieudé, Marine Forien, Blandine Pasquet, Chantal Job-Deslandre, Marine Meunier, Yannick Allanore, Service de Rhumatologie, AP-HP - Hôpital Bichat - Claude Bernard [Paris] - Université Paris Diderot - Paris 7 (UPD7) - PRES Sorbonne Paris Cité - AP-HP, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Institut Cochin (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), Investigation Clinique - Epidémiologie Clinique, AP-HP - Hôpital Bichat - Claude Bernard [Paris] - PRES Sorbonne Paris Cité - Institut National de la Santé et de la Recherche Médicale (INSERM) - AP-HP, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-PRES Sorbonne Paris Cité-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-PRES Sorbonne Paris Cité-Institut National de la Santé et de la Recherche Médicale (INSERM), BMC, Ed., and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité
Subjects: Adult, Male, medicine.medical_specialty, Immunology, Adipose tissue, Gastroenterology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Pharmacokinetics, Internal medicine, medicine, Humans, Immunology and Allergy, Spondylitis, Ankylosing, Spondylitis, Retrospective Studies, 030203 arthritis & rheumatology, 2. Zero hunger, Ankylosing spondylitis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Antibodies, Monoclonal, Retrospective cohort study, Middle Aged, medicine.disease, Infliximab, 3. Good health, Surgery, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Female, 030211 gastroenterology & hepatology, business, Body mass index, Research Article, medicine.drug
Abstract: Introduction The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. Methods In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. Results Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). Conclusions This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.
Published: 2012
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16. Independent replication and meta-analysis establish TNFSF4 as a susceptibility gene preferentially associated with the subset of patients with positive ACAs in SSc

Author: Coustet, B., Bouaziz, Maissa, Dieude, P., Guedj, Mickael, Bossini-Castillo, L., Gourh, P. R., Chiocchia, G., Allanore, Y., Université Paris Descartes - Paris 5 (UPD5), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), ProdInra, Migration, and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: tnfsf4, [INFO]Computer Science [cs], [MATH] Mathematics [math], [INFO] Computer Science [cs], [MATH]Mathematics [math], ComputingMilieux_MISCELLANEOUS, ssc
Abstract: International audience
Published: 2012

17. Evidence for the contribution of the X chromosome to SSc susceptibility: association with the functional IRAK1 196PHE/532SER haplotype

Author: Dieude, P., Bouaziz, Maissa, Riemekasten, G., Airo, P., Muller, M., Cusi, D., Chiocchia, G., Boileau, C., Allanore, Y., Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rheumatology and Clinical Immunology, Spedali Civili, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Università degli Studi di Milano = University of Milan (UNIMI), 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), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli Studi di Milano [Milano] (UNIMI), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [INFO]Computer Science [cs], [MATH]Mathematics [math], ComputingMilieux_MISCELLANEOUS, irak1, ssc
Abstract: Session 12 - Miscellaneous; International audience
Published: 2012

18. Timing and determinants of erythropoietin deficiency in chronic kidney disease. : Erythropoietin and chronic kidney disease

Author: Mercadal, Lucile, Metzger, Marie, Casadevall, Nicole, Haymann, Jean-Philippe, Karras, Alexandre, Boffa, Jean-Jacques, Flamant, Martin, Vrtovsnik, François, Stengel, Bénédicte, Froissart, Marc, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Physiologie [Tenon], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de Néphrologie [HEGP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Néphrologie [Bichat-Claude Bernard], Service de physiologie, explorations fonctionnelles et radioisotopes [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), The NephroTest CKD cohort study is supported by grants from: Inserm GIS-IReSP AO - 8113LS TGIR (BS), French Ministry of Health AOM 09114 (MF), Inserm AO 8022LS (BS), Agence de la Biomédecine R0 8156LL (BS), AURA (MF) and Roche 2009-152-447G (MF). The Nephrotest initiative was also sponsored by unrestricted grants from F.Hoffman-La Roche Ltd. (LM)., Nephrotest Study Group, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH : Male, MESH : Aged, MESH : Hemoglobins, MESH: Multivariate Analysis, MESH : Chronic Disease, hemic and lymphatic diseases, MESH : Erythropoietin, MESH : Middle Aged, MESH : Female, MESH: Erythropoietin, MESH: Aged, MESH: Kidney Diseases, MESH: Middle Aged, MESH: Humans, MESH: Chronic Disease, MESH: Time Factors, MESH : Humans, MESH : Glomerular Filtration Rate, MESH : Multivariate Analysis, MESH: Adult, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, MESH: Male, MESH: Glomerular Filtration Rate, MESH: Hemoglobins, MESH : Kidney Diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, MESH : Time Factors
Abstract: International audience; BACKGROUND AND OBJECTIVES: Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage CKD patients not receiving any erythropoiesis-stimulating agent. RESULTS: In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] 30 ml/min per 1.73 m(2), whereas they were not correlated when mGFR was 30 ml/min per 1.73 m(2) calls for other explanatory factors.
Published: 2012
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19. The thermolysin-like metalloproteinase and virulence factor LasB from pathogenic Pseudomonas aeruginosa induces anoikis of human vascular cells

Author: Beaufort, Nathalie, Corvazier, Elisabeth, Hervieu, Alexia, Choqueux, Christine, Dussiot, Michaël, Louedec, Liliane, Cady, Anne, Bentzmann, Sophie, Michel, Jean-Baptiste, Pidard, Dominique, Clinical Research Unit, Department of Obstetrics and Gynecology, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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)-Institut Galilée, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Technical University of Munich (TUM), 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 Diderot - Paris 7 (UPD7) - Université Paris 13 (UP13) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Institut Galilée, Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service de virologie, CHU Pontchaillou [Rennes] - Université de REnne, Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and CHU Pontchaillou [Rennes]-Université de REnne
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; Disruption of cell/ECM interactions resulting from uncontrolled pericellular proteolysis leads to detachment-induced cell apoptosis (anoikis), contributing to the morbid evolution of inflammatory vascular diseases. During cardiovascular infections, bacterial proteinases might induce vascular cells to enter a similar pathway. We focused on LasB, the predominant metalloproteinase secreted by the haematotropic pathogen Pseudomonas aeruginosa. While the exosecretome of the LasB-deficient pseudomonal strain PAO1lasB? had limited impact on human vascular cell adherence and viability, secretomes from the LasB-expressing reference strain, PAO1, or clinical isolates from patients with cardiac infection all induced anoikis, as did purified LasB. Immunofluorescence and/or immunoblotting analysis of heart valve myofibroblast cultures or whole tissue revealed an extensive, LasB-dependent degradation of ECM-associated fibronectin and vitronectin, that preceded cell de-adherence, whereas type I collagen showed limited degradation. Moreover, LasB produced a rapid endoproteolysis of the cell-associated urokinase receptor/uPAR, leaving a truncated receptor that is unable to support cell adherence and survival via interactions with vitronectin and integrins. Conversely, major myofibroblast integrins showed no or only minor alterations. Thus, among P. aeruginosa-secreted metalloproteinases, LasB can induce vascular cell anoikis through simultaneous proteolysis of ECM components and cell receptors, suggesting the uPAR-vitronectin axis as a major target in this process.
Published: 2011
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20. Basophils and Autoreactive IgE in the Pathogenesis of Systemic Lupus Erythematosus.: Basophils in Lupus

Author: Charles, Nicolas, Rivera, Juan, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Immunogenetics (LI-NIAMS), National Institutes of Health [Bethesda] (NIH)-National Institute of Arthritis, Musculoskeletal and Skin diseases, and The research of JR, reported herein, was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
Subjects: immune system diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, skin and connective tissue diseases
Abstract: International audience; Systemic lupus erythematosus (SLE) is a heterogeneous disease that can affect multiple organs. A hallmark of this disease, as is the case for other autoimmune diseases, is the presence of large numbers of autoantibodies. As such, SLE is considered to be a B-cell disease perpetuated by the expansion of autoreactive T and B cells. The T cells involved have long been considered to be T-helper type 1 (Th1) and Th17 cells, as these potent proinflammatory cells can be found in the tissues of SLE patients. Recent advances point to a role for the Th2 environment in contributing to SLE through promotion of autoantibody production. Here we describe the recent work focusing on autoreactive IgE and the activation of basophils as promoting the production of autoantibodies in SLE. The findings, both in a murine model of SLE and in humans with SLE, support the concept that the activation of the basophil by autoreactive IgE-containing immune complexes serves to amplify the production of autoantibodies and contributes to the pathogenesis of disease. We propose that therapeutic targeting of this amplification loop by reducing the levels of circulating autoreactive IgE may have benefit in SLE.
Published: 2011
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21. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis

Author: Valeria Riccieri, László Czirják, Yannick Allanore, Jean-Luc Cracowski, Catherine Boileau, Inga Melchers, H.-Erich Wichmann, Jean-Charles Lambert, Oliver Meyer, Julien Wipff, Mohamad Saad, Jörg H W Distler, Luc Mouthon, Anne Marie Dupuy, Costanza Conti, Martina Müller, Nicolas Hunzelmann, Maria Martinez, Marco Matucci-Cerinic, Elisabeth Diot, Ulf Müller-Ladner, Paola Caramaschi, Otylia Kowal-Bielecka, André Kahan, Erika Salvi, G. Riemekasten, Arnold Munnich, Paolo Airò, Luc Letenneur, Eric Hachulla, Kiet Tiev, Barbara Ruiz, Daniele Cusi, Jérôme Avouac, Nemanja Damjanov, Philippe Dieudé, Gabriele Valentini, Philippe Amouyel, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut 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), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine 3, Institute for Clinical Immunology Erlangen-Nuremberg, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Departments of Medicine, Biomedicine & Rheumatology, Università degli Studi di Firenze = University of Florence (UniFI)-Division of Rheumatology AOUC - Denothe Centre, Department of Rheumatology and Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rheumatology and Clinical Immunology, Spedali Civili, Clinical Research Unit for Rheumatology, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Service de médecine interne, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medicine, Surgery, and Dentistry, University of Milano, Genomics and Bioinformatics Platform, Fondazione Filarete, Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Institute of Epidemiology I, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Dermatology, University of Cologne, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rheumatology Unit, Università degli studi di Verona = University of Verona (UNIVR), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology and Internal Medicine, Medical University of Białystok (MUB), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Department of Immunology and Rheumatology, University of Pecs, Institute of Rheumatology, University of Belgrade [Belgrade], Kos Genetic SRL, Institute of Genetic Epidemiology, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Division of Rheumatology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This project was funded by Agence Nationale pour la Recherche (Project ANR-08-GENO-016-1) and supported by research grants from SERVIER research group, SANOFI-AVENTIS, Association des Sclérodermies de France, and Groupe Français de Recherche sur la Sclérodermie. The KORA (Cooperative health research in the Region of Augsburg) studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN). This research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. HYPERGENES (European Network for Genetic-Epidemiological Studies) is funded by EU within the FP7: HEALTH-F4-2007-201550., European Project: 201550,EC:FP7:HEALTH,FP7-HEALTH-2007-A,HYPERGENES(2008), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Division of Rheumatology AOUC - Denothe Centre-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Freiburg University Medical Center, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Verona (UNIVR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, University of Naples Federico II, German Research Center for Environmental Health, Justus-Liebig-Universität Gießen (JLU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Division of Rheumatology AOUC - Denothe Centre, Allanore, Y, Saad, M, Dieudé, P, Avouac, J, Distler, Jh, Amouyel, P, MATUCCI CERINIC, M, Riemekasten, G, Airo, P, Melchers, I, Hachulla, E, Cusi, D, Wichmann, He, Wipff, J, Lambert, Jc, Hunzelmann, N, Tiev, K, Caramaschi, P, Diot, E, KOWAL BIELECKA, O, Valentini, Gabriele, Mouthon, L, Czirják, L, Damjanov, N, Salvi, E, Conti, C, Müller, M, MÜLLER LADNER, U, Riccieri, V, Ruiz, B, Cracowski, Jl, Letenneur, L, Dupuy, Am, Meyer, O, Kahan, A, Munnich, A, Boileau, C, Martinez, M., Autard, Delphine, European Network for Genetic-Epidemiological Studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model - HYPERGENES - - EC:FP7:HEALTH2008-01-01 - 2011-12-31 - 201550 - VALID, and Service de médecine interne [CHU Saint-Antoine]
Subjects: Male, Cancer Research, Linkage disequilibrium, Epidemiology, systemic sclerosis, RHOB, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Linkage Disequilibrium, MESH: Scleroderma, Systemic, Scleroderma, Major Histocompatibility Complex, Disease Mapping, TNIP1 locus, 0302 clinical medicine, Germany, Genetics of the Immune System, HLA-DQ beta-Chains, MESH: Proteins, Connective Tissue Diseases, rhoB GTP-Binding Protein, Genetics (clinical), Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, 3. Good health, DNA-Binding Proteins, Europe, Italy, MESH: Linkage Disequilibrium, Genetic Epidemiology, Medicine, Cytokines, Female, Inflammatory and Psoriatic Arthritis, France, Research Article, Adult, lcsh:QH426-470, Medizinische Fakultät -ohne weitere Spezifikation, Rheumatoid Arthritis, Single-nucleotide polymorphism, Locus (genetics), Biology, Systemic Lupus Erythematosus, Polymorphism, Single Nucleotide, Autoimmune Diseases, 03 medical and health sciences, MESH: Major Histocompatibility Complex, Rheumatology, RhoB GTP-Binding Protein, functional polymorphism, extracellular-matrix, association, scleroderma, population, disease, susceptibility, fibrosis, receptor, stat4, Psoriasis, Humans, SNP, Genetic Predisposition to Disease, genome-wide scan, ddc:610, Molecular Biology, MESH: Germany, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, MESH: rhoB GTP-Binding Protein, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Scleroderma, Systemic, MESH: Humans, Proteins, MESH: Italy, MESH: Adult, MESH: HLA-DQ beta-Chains, MESH: Male, MESH: France, lcsh:Genetics, Immune System, Case-Control Studies, Immunology, MESH: Genome-Wide Association Study, Clinical Immunology, MESH: Europe, MESH: Female, MESH: DNA-Binding Proteins, Genome-Wide Association Study
Abstract: Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P, Author Summary Systemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy, severe immunologic alterations, and massive deposits of matrix components in the connective tissue. Epidemiological investigations indicate that SSc follows a pattern of multifactorial inheritance; however, only a few loci have been replicated in multiple studies. We undertook a two-stage genome-wide association study of SSc involving over 8,800 individuals of European ancestry. Combined analyses showed independent association at the known HLA-DQB1 region and revealed associations at PSORS1C1, TNIP1, and RHOB loci, in agreement with a strong immune genetic component. Because of its biological relevance, and previous reports of genetic association at this locus with other connective tissue disorders, we investigated TNIP1 expression. We observed a markedly reduced expression of the gene and its protein product in SSc, as well as its potential implication in control of extra-cellular matrix synthesis, providing a new clue for a link between inflammation/immunity and fibrosis.
Published: 2011
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22. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia

Author: Damien Grapton, Marie-Alexandra Alyanakian, Virginie Pascal, Michael Dussiot, Tomas Leanderson, Thiago Trovati Maciel, Olivier Hermine, Marc Benhamou, Séverine Coulon, Renato C. Monteiro, Patrick Mayeux, Kamel Djedaini, Zeliha Oruc, Julie Vandekerckhove, Saurabh Agarwal, Meetu Kaushik Tiwari, Michel Cogné, Ivan C. Moura, Bertrand Arnulf, Houda Tamouza, Geneviève Courtois, Aurélie Fricot, Pamella Huey Mei Wang, Yael Zermati, Jean-Antoine Ribeil, Céline Callens, Cytokines, hématopoïèse et réponse immune (CHRI), 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), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), 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)-Institut Galilée, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Différenciation des cellules B, hémopathies, lymphoïdes et déficit de l'immunité humorale, Université Paris Diderot - Paris 7 (UPD7), Tolérance immunitaire et présentation antigénique: impact en auto-immunité et en transplantation, Institut Cochin (UMR_S567 / UMR 8104), Université de Limoges (UNILIM), Service d Hématologie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), 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 ) -Institut Galilée, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université de Limoges ( UNILIM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Slama, Catherine
Subjects: Ineffective erythropoiesis, MESH: Signal Transduction, MESH: Anemia, Erythroblasts, MESH: Mice, Inbred NOD, MESH: Anoxia, Mice, SCID, medicine.disease_cause, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Mice, Inbred NOD, hemic and lymphatic diseases, MESH : Cell Proliferation, MESH : Erythropoietin, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Erythropoiesis, MESH: Animals, MESH: Mice, SCID, MESH: Erythroblasts, Hypoxia, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, Transferrin, Anemia, General Medicine, MESH : Transferrin, MESH : Mice, Transgenic, 3. Good health, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Mitogen-Activated Protein Kinases, MESH: Transferrin, medicine.drug, Signal Transduction, MESH: Cells, Cultured, MESH : Anoxia, MESH: Mice, Transgenic, MESH : Anemia, Transferrin receptor, Mice, Transgenic, MESH : Immunoglobulin A, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, MESH : Erythropoiesis, Erythroblast, MESH: Cell Proliferation, Receptors, Transferrin, MESH : Mice, MESH : Cells, Cultured, medicine, Animals, Humans, MESH : Receptors, Transferrin, MESH: Receptors, Transferrin, MESH: Erythropoietin, MESH: Immunoglobulin A, Erythropoietin, MESH: Mice, PI3K/AKT/mTOR pathway, 030304 developmental biology, Cell Proliferation, MESH : Signal Transduction, MESH: Humans, MESH : Mice, Inbred NOD, MESH : Humans, MESH: Erythropoiesis, MESH : Mitogen-Activated Protein Kinases, MESH : Phosphatidylinositol 3-Kinases, MESH : Erythroblasts, medicine.disease, MESH: Mitogen-Activated Protein Kinases, MESH : Mice, SCID, Immunoglobulin A, chemistry, MESH: Phosphatidylinositol 3-Kinases, Immunology, Cancer research, MESH : Animals
Abstract: International audience; Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXXΦ. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.
Published: 2011
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23. Critical role of the neutrophil-associated high affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

Author: Pierre-Henri Commere, Michel Dy, Salaheddine Mécheri, Cedric Mathieu, Jacques A. Louis, Geneviève Milon, Julien Claver, Hélène Kiefer-Biasizzo, Hajime Karasuyama, Jean-Pierre Kinet, Adeline Porcherie, Elke Schneider, Roger Peronet, Ulrich Blank, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Biologie des Interactions Hôte-Parasite, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagopole (CITECH), Institut Pasteur [Paris] (IP), Tokyo Medical and Dental University [Japan] (TMDU), Immunophysiologie et Parasitisme Intracellulaire, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), and Slama, Catherine
Subjects: Adoptive cell transfer, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neutrophils, Plasmodium berghei, medicine.medical_treatment, Immunology, Population, Malaria, Cerebral, Immunoglobulin E, Article, Proinflammatory cytokine, Pathogenesis, 03 medical and health sciences, Mice, 0302 clinical medicine, parasitic diseases, medicine, Immunology and Allergy, Animals, Protein Isoforms, education, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mice, Knockout, 0303 health sciences, education.field_of_study, biology, Receptors, IgE, fungi, biology.organism_classification, Adoptive Transfer, 3. Good health, Basophils, Eosinophils, Mice, Inbred C57BL, Cytokine, Cerebral Malaria, biology.protein, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030215 immunology
Abstract: FcεR1-expressing neutrophils accumulate in the brain of mice infected with Plasmodium berghei (PbANKA) and promote the development of experimental cerebral malaria., The role of the IgE–FcεRI complex in malaria severity in Plasmodium falciparum–hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-expressing effector cells, are not involved in disease as mast cell–deficient and basophil-depleted mice developed a disease similar to wild-type mice. However, we show the emergence of an FcεRI+ neutrophil population, which is not observed in mice hosting a non–ECM-inducing PbNK65 parasite strain. Depletion of this FcεRI+ neutrophil population prevents ECM, whereas transfer of this population into FcεRIα-KO mice restores ECM susceptibility. FcεRI+ neutrophils preferentially home to the brain and induce elevated levels of proinflammatory cytokines. These data define a new pathogenic mechanism of ECM and implicate an FcεRI-expressing neutrophil subpopulation in malaria disease severity.
Published: 2011
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24. A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

Author: Yves Lepelletier, Ivan C. Moura, Bertrand Arnulf, Marc Benhamou, Renato C. Monteiro, Olivier Hermine, Patrick England, Cédric Baude, Ali Bazarbachi, Carole Beaumont, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Department of hematology, university of Beiruth, CHU Necker - Enfants Malades [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), International University of Beirut (BIU), Supported by grants from Arecca and la Ligue contre le Cancer. I.C.M. and Y.L. were both recipients of la Ligue contre le Cancer fellowship., ENGLAND, Patrick, BMC, Ed., Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: MESH: Cell Death, T-Lymphocytes, [SDV]Life Sciences [q-bio], Apoptosis, MESH: Flow Cytometry, Lymphocyte Activation, Biochemistry, MESH: Antibodies, Monoclonal, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, hemic and lymphatic diseases, MESH: Microscopy, Confocal, IL-2 receptor, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Human T-lymphotropic virus 1, MESH: Iron, 0303 health sciences, Microscopy, Confocal, Cell Death, MESH: Kinetics, Transferrin, Antibodies, Monoclonal, Hematology, Flow Cytometry, MESH: Surface Plasmon Resonance, 3. Good health, [SDV] Life Sciences [q-bio], [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Leukocytes, Mononuclear, Leukemia, Infectious Diseases, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Cell Division, Antibody, Cell Division, MESH: Transferrin, Protein Binding, MESH: Leukemia, T-Cell, medicine.drug, lcsh:Immunologic diseases. Allergy, Interleukin 2, Leukemia, T-Cell, medicine.drug_class, Iron, Immunology, Transferrin receptor, Biology, Endocytosis, Monoclonal antibody, MESH: Receptors, Interleukin-2, 03 medical and health sciences, Virology, Receptors, Transferrin, medicine, Humans, MESH: Protein Binding, MESH: Receptors, Transferrin, MESH: Lymphocyte Activation, 030304 developmental biology, MESH: Human T-lymphotropic virus 1, MESH: Humans, Dose-Response Relationship, Drug, MESH: Apoptosis, Germinal center, Receptors, Interleukin-2, Cell Biology, Surface Plasmon Resonance, medicine.disease, Molecular biology, Kinetics, MESH: T-Lymphocytes, chemistry, Meeting Abstract, Leukocytes, Mononuclear, biology.protein, Cancer research, lcsh:RC581-607, Ex vivo, 030215 immunology
Abstract: International audience; Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoid proliferative disease that exists under diverse clinical forms ranging from chronic to acute. Although leukemic cells from patients with ATL exhibit an intrinsic resistance to chemotherapy, monoclonal antibodies directed against CD25 (interleukin 2 receptor ␣ [IL-2R␣] antibody) have been used as specific therapeutic agents. However, significant clinical results with these antibodies have been demonstrated only in chronic forms of ATL. In contrast to resting T cells, human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells constitutively express high levels of surface transferrin receptor (TfR). Herein, we report the characterization of a new monoclonal antibody (mAb A24) directed against the human TfR and the evaluation of its capacity to block the proliferation of ATL cells ex vivo. We determined that A24 binds TfR with an equilibrium constant (K d) of 2.7 nM and competes with transferrin for binding to TfR. A24 also inhibited [ 55 Fe]-transferrin uptake in activated T cells and blocked T-cell proliferation. Moreover, A24 reduced and impaired TfR expression and recycling, respectively. Most important, we showed that A24 blocked the ex vivo proliferation of malignant T cells from both acute and chronic forms of ATL, through induction of programmed cell death. Therefore efficient therapeutic tools to treat acute forms of ATL might be derived from A24.
Published: 2011
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25. Breast milk immune complexes are potent inducers of oral tolerance in neonates and prevent asthma development

Author: Eric Mosconi, Akira Kanda, Barbara Seitz-Polski, Sébastien Fleury, Akila Rekima, Nicolas Glaichenhaus, Valérie Verhasselt, Renato C. Monteiro, Valérie Julia, David Dombrowicz, Emilie Tissandie, Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Schistosomiase, paludisme et inflammation, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Lille Nord de France (COMUE), Réseau International des Instituts Pasteur (RIIP), Immunopathologie rénale, récepteurs et inflammation, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Asthma, MESH: Interleukin-2 Receptor alpha Subunit, Administration, Oral, Antigen-Antibody Complex, Receptors, Fc, T-Lymphocytes, Regulatory, MESH: Mice, Knockout, MESH: Animals, Newborn, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Immunology and Allergy, MESH: Animals, IL-2 receptor, MESH: Maternal Exposure, Mice, Knockout, MESH: Immunoglobulin G, Mice, Inbred BALB C, 0303 health sciences, MESH: Milk, Human, FOXP3, Forkhead Transcription Factors, MESH: Antigen-Antibody Complex, 3. Good health, Tolerance induction, Breast Feeding, Maternal Exposure, MESH: Breast Feeding, MESH: Administration, Oral, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Receptors, Fc, MESH: Allergens, MESH: Immune Tolerance, Ovalbumin, Immunology, MESH: Mice, Inbred BALB C, Breast milk, 03 medical and health sciences, Immune system, Neonatal Fc receptor, Antigen, MESH: Mice, Inbred C57BL, MESH: Forkhead Transcription Factors, Immune Tolerance, medicine, Animals, MESH: Mice, 030304 developmental biology, Asthma, MESH: Ovalbumin, Milk, Human, business.industry, MESH: T-Lymphocytes, Regulatory, Histocompatibility Antigens Class I, Interleukin-2 Receptor alpha Subunit, Allergens, medicine.disease, MESH: Male, Mice, Inbred C57BL, Animals, Newborn, Immunoglobulin G, MESH: Immunity, Maternally-Acquired, business, Immunity, Maternally-Acquired, MESH: Female, 030215 immunology
Abstract: International audience; Allergic asthma is a chronic lung disease resulting from an inappropriate T helper (Th)-2 response to environmental antigens. Early tolerance induction is an attractive approach for primary prevention of asthma. Here, we found that breastfeeding by antigen-sensitized mothers exposed to antigen aerosols during lactation induced a robust and long-lasting antigen-specific protection from asthma. Protection was more profound and persistent than the one induced by antigen-exposed non-sensitized mothers. Milk from antigen-exposed sensitized mothers contained antigen-immunoglobulin (Ig) G immune complexes that were transferred to the newborn through the neonatal Fc receptor resulting in the induction of antigen-specific FoxP3(+) CD25(+) regulatory T cells. The induction of oral tolerance by milk immune complexes did not require the presence of transforming growth factor-beta in milk in contrast to tolerance induced by milk-borne free antigen. Furthermore, neither the presence of IgA in milk nor the expression of the inhibitory FcgammaRIIb in the newborn was required for tolerance induction. This study provides new insights on the mechanisms of tolerance induction in neonates and highlights that IgG immune complexes found in breast milk are potent inducers of oral tolerance. These observations may pave the way for the identification of key factors for primary prevention of immune-mediated diseases such as asthma.
Published: 2010
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26. The Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane

Author: Marion Zarka, Ivan C. Moura, Bénédicte Py, Marc Benhamou, Hakim Hocini, Jérôme Bouchet, Serge Benichou, Ricardo Madrid, Stéphane Basmaciogullari, Renato C. Monteiro, DUTOIT, Soizic, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unite de Recherches en Immunologie Humaine, and Université de Montréal (UdeM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Phospholipid scramblase, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, [SDV]Life Sciences [q-bio], Cell, HIV Infections, Biology, Jurkat Cells, Cell Biology/Membranes and Sorting, Viral entry, Virology, medicine, Humans, Secretory Leukocyte Peptidase Inhibitor, Phospholipid Transfer Proteins, Receptor, chemistry.chemical_classification, Multidisciplinary, Cell Membrane, Cell Biology, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, chemistry, Membrane protein, Virology/Viral Replication and Gene Regulation, Cytoplasm, Virology/Immunodeficiency Viruses, CD4 Antigens, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Glycoprotein, SLPI, Research Article, Protein Binding
Abstract: Erratum inPLoS ONE. 2009;4(4). doi: 10.1371/annotation/657cd713-aaac-4ebb-80ad-3ec8dfb12b42; International audience; Secretory leukocyte protease inhibitor (SLPI) is secreted by epithelial cells in all the mucosal fluids such as saliva, cervical mucus, as well in the seminal liquid. At the physiological concentrations found in saliva, SLPI has a specific antiviral activity against HIV-1 that is related to the perturbation of the virus entry process at a stage posterior to the interaction of the viral surface glycoprotein with the CD4 receptor. Here, we confirm that recombinant SLPI is able to inhibit HIV-1 infection of primary T lymphocytes, and show that SLPI can also inhibit the transfer of HIV-1 virions from primary monocyte-derived dendritic cells to autologous T lymphocytes. At the molecular level, we show that SLPI is a ligand for the phospholipid scramblase 1 (PLSCR1) and PLSCR4, membrane proteins that are involved in the regulation of the movements of phospholipids between the inner and outer leaflets of the plasma membrane. Interestingly, we reveal that PLSCR1 and PLSCR4 also interact directly with the CD4 receptor at the cell surface of T lymphocytes. We find that the same region of the cytoplasmic domain of PLSCR1 is involved in the binding to CD4 and SLPI. Since SLPI was able to disrupt the association between PLSCR1 and CD4, our data suggest that SLPI inhibits HIV-1 infection by modulating the interaction of the CD4 receptor with PLSCRs. These interactions may constitute new targets for antiviral intervention.
Published: 2009
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27. Vesicle associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells

Author: Leif E. Sander, Ulrich Blank, Axel Lorentz, Hans Bigalke, Thierry Galli, Stephan C. Bischoff, Seza Bolat, Simon P.C. Frank, Institute of Nutritional Medicine, University of Hohenheim, University of Hohenheim, Department of Medicine III, University hospital (UKA), University of Aachen (RWTH), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH)-University hospital (UKA), Department of Gastroenterology, Hepatology and Endocrinology (MHH), Hannover Medical School [Hannover] (MHH), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), INSERM ERL U950, Membrane Traffic in Neuronal and Epithelial Morphogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Toxicology, Medical School of Hannover, and Trafic membranaire et morphogenèse neuronale et épithéliale (Resp T. Galli)
Subjects: Cytoplasm, Vesicle-Associated Membrane Protein 3, Vesicle-Associated Membrane Protein 2, MESH: R-SNARE Proteins, Fluorescent Antibody Technique, Gene Expression, Immunoglobulin E, Histamine Release, Cell Degranulation, R-SNARE Proteins, chemistry.chemical_compound, Mucosal immunity, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Qa-SNARE Proteins, Immunology and Allergy, Syntaxin, Mast Cells, Receptor, MESH: Fluorescent Antibody Technique, MESH: Vesicle-Associated Membrane Protein 3, MESH: Vesicle-Associated Membrane Protein 2, 0303 health sciences, biology, MESH: Qc-SNARE Proteins, Qa-SNARE Proteins, Reverse Transcriptase Polymerase Chain Reaction, 030302 biochemistry & molecular biology, Degranulation, Metalloendopeptidases, MESH: Mast Cells, Qb-SNARE Proteins, Cell biology, Blot, Vesicle-associated membrane protein, Allergology, MESH: Cell Degranulation, [SDV.IMM]Life Sciences [q-bio]/Immunology, SNARE Proteins, Histamine, MESH: SNARE Proteins, MESH: Gene Expression, Immunology, Blotting, Western, MESH: Metalloendopeptidases, Antibodies, 03 medical and health sciences, Tetanus Toxin, MESH: Qb-SNARE Proteins, MESH: Blotting, Western, Humans, Qc-SNARE Proteins, MESH: Tetanus Toxin, 030304 developmental biology, MESH: Histamine Release, MESH: Humans, MESH: Antibodies, MESH: Cytoplasm, Cell Membrane, Cellular immunology, Lipid bilayer fusion, chemistry, biology.protein, MESH: Cell Membrane
Abstract: International audience; Mediator release from mast cells (MC) is a crucial step in allergic and non-allergic inflammatory disorders. However, the final events in response to activation leading to membrane fusion and thereby facilitating degranulation have hitherto not been analyzed in human MC. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNARE) represent a highly conserved family of proteins that have been shown to mediate intracellular membrane fusion events. Here, we show that mature MC isolated from human intestinal tissue express soluble N-ethylmaleide sensitive factor attachment protein (SNAP)-23, Syntaxin (STX)-1B, STX-2, STX-3, STX-4, and STX-6 but not SNAP-25. Furthermore, we found that primary human MC express substantial amounts of vesicle associated membrane protein (VAMP)-3, VAMP-7 and VAMP-8 and, in contrast to previous reports about rodent MC, only low levels of VAMP-2. Furthermore, VAMP-7 and VAMP-8 were found to translocate to the plasma membrane and interact with SNAP-23 and STX-4 upon activation. Inhibition of SNAP-23, STX-4, VAMP-7 or VAMP-8, but not VAMP-2 or VAMP-3, resulted in a markedly reduced high-affinity IgE receptor-mediated histamine release. In summary, our data show that mature human MC express a specific pattern of SNARE and that VAMP-7 and VAMP-8, but not VAMP-2, are required for rapid degranulation.
Published: 2008
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28. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease.: IgA retrotranscytosis in celiac disease

Author: Matysiak-Budnik, Tamara, Cruz-Moura, Ivan, Arcos-Fajardo, Michelle, Lebreton, Corinne, Ménard, Sandrine, Candalh, Céline, Ben Khalifa, Karima, Dugave, Christophe, Tamouza, Houda, Van Niel, Guillaume, Bouhnik, Yoram, Lamarque, Dominique, Chaussade, Stanislas, Malamut, Georgia, Cellier, Christophe, Cerf-Bensussan, Nadine, Monteiro, Renato, Heyman, Martine, Interactions de l'épithelium intestinal avec le système immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Compartimentation et dynamique cellulaires ( CDC ), Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: MESH : Molecular Weight, MESH : Immunohistochemistry, MESH : Immunoglobulin A, MESH : Models, Biological, MESH: Glomerulonephritis, IGA, digestive system, MESH : Gliadin, MESH : Chromatography, High Pressure Liquid, MESH: Biopsy, MESH: Enterocytes, MESH : Antigens, CD, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Receptors, Transferrin, MESH: Receptors, Transferrin, MESH: Immunoglobulin A, intestinal transport, MESH: Chromatography, High Pressure Liquid, MESH: Antigens, CD, Ussing chamber, MESH: Humans, MESH : Peptides, MESH: Peptides, MESH: Molecular Weight, MESH : Humans, MESH: Models, Biological, food and beverages, nutritional and metabolic diseases, MESH: Gliadin, MESH: Immunohistochemistry, MESH : Celiac Disease, transferrin receptor, digestive system diseases, MESH : Enterocytes, gliadin peptides, MESH : Biopsy, receptor-mediated transcytosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Glomerulonephritis, IGA, celiac disease, IgA, MESH: Celiac Disease
Abstract: International audience; Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA-gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA-gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
Published: 2008
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29. 9-Phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels

Author: Grand, Teddy, Demion, Marie, Norez, Caroline, Mettey, Yvette, Launay, Pierre, Becq, Frédéric, Bois, Patrick, Guinamard, Romain, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe coeur et ischémie, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)
Subjects: Patch-Clamp Techniques, TRPM4, TRPM5, cation channel, TRPM Cation Channels, CHO Cells, Phenanthrenes, Transfection, Research Papers, Cell Line, Inhibitory Concentration 50, Cricetulus, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Cricetinae, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Animals, Humans, benzo[c]quinolizinium, CFTR, Quinolizines, 9-phenanthrol
Abstract: (IF : 3,76); International audience; TRPM4 and TRPM5 are calcium-activated non-selective cation channels with almost identical characteristics. TRPM4 is detected in several tissues including heart, kidney, brainstem, cerebral artery and immune system whereas TRPM5 expression is more restricted. Determination of their roles in physiological processes requires specific pharmacological tools. TRPM4 is inhibited by glibenclamide, a modulator of ATP binding cassette proteins (ABC transporters), such as the cystic fibrosis transmembrane conductance regulator (CFTR). We took advantage of this similarity to investigate the effect of hydroxytricyclic compounds shown to modulate ABC transporters, on TRPM4 and TRPM5. EXPERIMENTAL APPROACH: Experiments were conducted using HEK-293 cells permanently transfected to express human TRPM4 or TRPM5. Currents were recorded using the whole-cell and inside-out variants of the patch-clamp technique. KEY RESULTS: The CFTR channel activator benzo[c]quinolizinium MPB-104 inhibited TRPM4 current with an IC(50) in the range of 2 x 10(-5) M, with no effect on single-channel conductance. In addition, 9-phenanthrol, lacking the chemical groups necessary for CFTR activation, also reversibly inhibited TRPM4 with a similar IC(50). Channel inhibition was voltage independent. The IC(50) determined in the whole-cell and inside-out experiments were similar, suggesting a direct effect of the molecule. However, 9-phenanthrol was ineffective on TRPM5, the most closely related channel within the TRP protein family.CONCLUSIONS AND IMPLICATIONS: We identify 9-phenanthrol as a TRPM4 inhibitor, without effects on TRPM5. It could be valuable in investigating the physiological functions of TRPM4, as distinct from those of TRPM5.
Published: 2008
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30. Effects of radionuclides (uranium et cesium 137) on vitamin D in rat

Author: Tissandie, Emilie, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Blaise Pascal - Clermont-Ferrand II, Université d'Auvergne - Clermont-Ferrand I, Souidi Maamar, and Meyer, Camille
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, vitamine D, rat, [SDV.GEN] Life Sciences [q-bio]/Genetics, écotoxicologie, radionucléides
Abstract: The aim of this work was to investigate the effects of depleted (DU) or enriched uranium (EU) and of cesium 137 (137Cs) on vitamin D3 biosynthetic pathway in liver, kidney and brain in rat. A chronic exposure with environmental doses of 137Cs and uranium could decrease the vitamin D active form level (1,25(OH)2D3) and lead to molecular modifications of cytochromes P450 (CYPs) enzymes involved in this metabolism and associated nuclear receptors. We demonstrated that both UA and UE contamination affected VDR (vitamin D receptor) and RXRα (retinoid X receptor alpha) expression, and consequently could modulate the expression of vitamin D target genes involved in calcium homeostasis in kidney (ecac1, Epithelials Ca2+ channel 1 et cabp-d28k, Calbindin-D28K). These results suggest that these effects could be due to the chemical toxicity of uranium. On the contrary, the main molecular targets of 137Cs are CYPs involved in Vitamin D3 biosynthesis (CYP2R1, CYP27B1) in liver and brain., Les objectifs de ce travail étaient d'évaluer les effets de l'uranium appauvri (UA) ou enrichi (UE) et du césium 137 (137Cs) sur le métabolisme de la vitamine D au niveau du foie, du rein et du système nerveux central chez le rat. Une exposition chronique à de faibles doses d'UA ou de 137Cs diminue le taux de vitamines D active (1,25(OH)2D3) et entraîne des modifications moléculaires des enzymes de types cytochromes P450 (CYPs) impliqués dans ce métabolisme et des récepteurs nucléaires associés. Nous avons démontré qu'une contamination à l'UA et à l'UE affectent de la même manière l'expression de VDR (vitamin D receptor) et de RXRalpha (retinoic X receptor alpha) et par conséquent peuvent moduler l'expression des gènes cibles de la vitamine D impliqués dans le transport du calcium au niveau rénal (ecac 1, Epithelials Ca2+ channel 1 et cabp-d28k, Calbindin-D28K). Ces résultats suggèrent que ces effets sont dus à la toxicité chimique de l'uranium. A l'inverse, les principales cibles moléculaires du 137Cs sont les CYPs qui sont impliquées dans la biosynthèse de la vitamine D (CYP2R1, CYP27B1) au niveau du foie et du système nerveux
Published: 2007

31. [Renal and urinary tract disease national research program]

Author: Stengel, Bénédicte, Antignac, Corinne, Baverel, Gabriel, Choukroun, Gabriel, Cussenot, Olivier, Dussaule, Jean-Claude, Friedlander, Gérard, Lang, Philippe, Lelièvre-Pégorier, Martine, Massy, Ziad, Monteiro, Renato, Parini, Angelo, Soulillou, Jean Paul, Baud, Laurent, Ronco, Pierre, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Métabolomique et maladies métaboliques, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de médecine, RTH Laennec, Université de Picardie Jules Verne (UPJV), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de transplantation et de recherche en transplantation (ITERT), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Remodelage et Reparation du Tissu Renal, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie, CHU Amiens-Picardie, CHU Tenon [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de transplantation et de recherche en transplantation ( ITERT ), Université de Nantes ( UN ), and Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ITUN
Subjects: Urologic Diseases, MESH: Kidney Diseases, MESH: Humans, MESH : Urologic Diseases, Incidence, Research, MESH : Foundations, MESH : Humans, MESH : Research, Kidney Transplantation, MESH : Incidence, MESH: Urologic Diseases, MESH: Kidney Transplantation, MESH: France, MESH: Research, MESH: Foundations, MESH : Kidney Diseases, Humans, MESH : Kidney Transplantation, Kidney Diseases, France, MESH: Incidence, MESH : France, Foundations
Abstract: International audience; The National Institute of Health and Medical Research (Inserm), the Society of Nephrology, and the French Kidney Foundation recognized the need to create a National Research Program for kidney and urinary tract diseases. They organized a conference gathering 80 researchers to discuss the state-of-the art and evaluate the strengths and weaknesses of kidney and urinary tract disease research in France, and to identify research priorities. From these priorities emerged 11 of common interest: 1) conducting epidemiologic studies; 2) conducting large multicenter cohorts of well-phenotyped patients with blood, urine and biopsy biobanks; 3) developing large scale approach: transcriptomics, proteomics, metabolomics; 4) developing human and animal functional imaging techniques; 5) strengthening the expertise in renal pathology and electrophysiology; 6) developing animal models of kidney injury; 7) identifying nontraumatic diagnostic and prognostic biomarkers; 8) increasing research on the fetal programming of adult kidney diseases; 9) encouraging translational research from bench to bedside and to population; 10) creating centers grouping basic and clinical research workforces with critical mass and adequate logistic support; 11) integrating and developing european research programs.
Published: 2007
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32. Mast cells and inflammatory kidney disease

Author: Ulrich Blank, Lisa Scandiuzzi, Yutaka Kanamaru, Marc Benhamou, Marie Essig, Blank, Ulrich, Immunopathologie rénale, récepteurs et inflammation, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunology, 030232 urology & nephrology, Inflammation, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, Mast Cells, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, 0303 health sciences, Nephritis, business.industry, Chymase, Glomerulonephritis, medicine.disease, Fibrosis, Angiotensin II, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Tubulointerstitial fibrosis, Nephritis, Interstitial, medicine.symptom, business, Homeostasis, Kidney disease
Abstract: International audience; Inflammatory kidney disease involves a complex network of interactions between resident kidney and infiltrating hematopoietic cells. Mast cells (MCs) are constitutively found in kidneys in small numbers but increase considerably in various renal diseases. While this increase is usually interpreted as a sign of pathological involvement, recent data using MC‐deficient animals show their ability to restore kidney homeostasis. In anti‐glomerular basement membrane antibody‐induced glomerulonephritis, MCs are protective by initiating repair and remodeling functions counteracting the devastating effects of glomerular injury. Protection may also include immunoregulatory capacities to limit autoreactive T‐cell responses. MCs also control tubulointerstitial fibrosis by activating tissue remodeling and neutralizing fibrotic factors. Release of mediators by MCs during inflammation, however, could also promote unwanted responses that ultimately lead to destruction of kidney structure, as exemplified by data showing either protection or aggravation in related renal disease models. Similarly, while the action of proteases may initially be beneficial, the generation of fibrosis‐promoting angiotensin II by chymase also shows the limits of adaptive responses to achieve homeostasis. Thus, it is likely the physiological context involving the interaction with other cells and inflammatory mediators that determines the final action of MCs in the development of kidney disease.
Published: 2007
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33. Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene

Author: Steven, Gazal, Karim, Sacre, Yannick, Allanore, Maria, Teruel, Alison H, Goodall, Shigeto, Tohma, Lars, Alfredsson, Yukinori, Okada, Gang, Xie, Arnaud, Constantin, Alejandro, Balsa, Aya, Kawasaki, Pascale, Nicaise, Christopher, Amos, Luis, Rodriguez-Rodriguez, Gilles, Chiocchia, Catherine, Boileau, Jinyi, Zhang, Olivier, Vittecoq, Thomas, Barnetche, Miguel A, Gonzalez Gay, Hiroshi, Furukawa, Alain, Cantagrel, Xavier, Le Loët, Takayuki, Sumida, Margarita, Hurtado-Nedelec, Christophe, Richez, Sylvie, Chollet-Martin, Thierry, Schaeverbeke, Bernard, Combe, Liliane, Khoryati, Baptiste, Coustet, Jammel, El-Benna, Katherine, Siminovitch, Robert, Plenge, Leonid, Padyukov, Javier, Martin, Naoyuki, Tsuchiya, Philippe, Dieudé, Plateforme de Génomique Constitutionnelle, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut 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), Spanish National Research Council (CSIC), University of Leicester, Université de Tsukuba = University of Tsukuba, Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Toronto, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], University Hospital La Paz, Madrid, Service d'Immunologie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris (AP-HP)-Assistance Publique-Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Dartmouth College [Hanover], Rheumatology Service, Hospital Clínico San Carlos, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hospital Marques de Valdecillas, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Service d'hématologie et immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Département Hospitalo-Universitaire (DHU), Merck & Co. Inc, Rheumatology Unit, Department of Medicine, Karolinska Institutet [Stockholm], P.D. is supported by a grant fromthe French Society of Rheumatology.K.S.was fundedbythe Canadian Institutes forHealth Research grant MOP79321andsupported bythe CanadaResearch ChairY.O. is supported by a grant from the Japan Society of the Promotion ofScience (JSPS).EIRA study was supported by AFA, The Swedish Research Council,VINNOVA, King Gustaf V Foundation and EU grants (Autocure and BeTheCure).TheSpanish biobank was partially funded by the RETICS Program, RD08/0075 (RIER) from theInstituto de Salud Carlos III(ISCIII), within the VI PN de I+D+i 2008-2011. The ESPOIRcohort was supported byan unrestricted grant from Merck Sharp and Dohme (MSD),ABBOTT,WYETH-PFIZER,ROCHE, INSERM and The French Society of Rheumatology.The FRAGC biobank wassupported byan unrestricted grant from ROCHE, PFIZER andUCB., Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité-Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Cochin ( 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 ), Spanish National Research Council ( CSIC ), University of Tsukuba, Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston] ( MGH ) -Massachusetts Institute of Technology ( MIT ), Assistance Publique-Hôpitaux de Paris (AP-HP)-Assistance Publique-Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rhumatologie [Rouen], Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Rouen, Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Broad Institute of MIT and Harvard, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Gazal, Steven, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Immunology, Rheumatoid Arthritis, Susceptibility gene, [SDV.GEN] Life Sciences [q-bio]/Genetics, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Gene Polymorphism, Rheumatology, Genotype, medicine, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Allele, Alleles, Autoantibodies, 030304 developmental biology, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, biology, Macrophages, Odds ratio, medicine.disease, 3. Good health, Haplotypes, Ant-CCP, Case-Control Studies, Rheumatoid arthritis, Expression quantitative trait loci, biology.protein, Citrulline, Female, Osteopontin, Antibody, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Peptides, Secreted Phosphoprotein 1 Gene
Abstract: International audience; Objective To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the RA genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. Methods We analyzed a total of 11,715 RA cases and 26,493 controls from 9 independent cohorts, all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on OPN expression in macrophages and OPN serum levels was investigated. Results We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥ 3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (P = 1.29x10-5, ORACPA-negative 1.257 1.135–1.394) and less with ACPA positivity (P = 0.0148, ORACPA-positive 1.072 1.014–1.134]). The odds ratios between these subgroups (i.e., ACPA-positive and -negative) significantly differed (P = 7.33x10-3). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (P = 0.0157) as well as serum level of secreted OPN correlated positively with ACPA production (P = 0.005; r = 0.483). Conclusion We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association greater in patients negative for ACPAs.
Published: 2014
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34. Rituximab versus azathioprine for ANCA-associated vasculitis maintenance therapy: Impact on global disability and health-related quality of life

Author: Pugnet, G., Pagnoux, C., Terrier, B., Elodie Perrodeau, Puéchal, X., Karras, A., Khouatra, C., Aumaître, O., Cohen, P., Maurier, F., Decaux, O., Ninet, J., Gobert, P., Quemeneur, T., Blanchard-Delaunay, C., Godmer, P., Carron, P. -L, Hatron, P. -Y, Limal, N., Hamidou, M., Ducret, M., Daugas, E., Papo, T., Bonnotte, B., Mahr, A., Ravaud, P., Mouthon, L., Guillevin, L., Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] ( DHU - I2B ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Pitié-Salpêtrière [APHP], Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service de médecine interne, hôpital Gabriel-Montpied, CHU Clermont-Ferrand, Service de médecine interne, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), 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 ), Service de Médecine Interne, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Département de Médecine Interne ( VALENCIENNES - Med Int ), CH Valenciennes, Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de médecine interne [Nantes], Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Bichat - Claude Bernard, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), 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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Médecine Interne (VALENCIENNES - Med Int), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Rennes 1 (UR1), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Jonchère, Laurent, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville)-Hôpital Sainte-Blandine, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Middle Aged, [SDV] Life Sciences [q-bio], Azathioprine, Quality of Life, Humans, Disabled Persons, Female, Rituximab, Aged
Abstract: IF 2.724 (2014); International audience; OBJECTIVES: To investigate the effects on health-related quality of life (HRQOL) and functional capability of rituximab vs azathioprine for ANCA-associated vasculitis (AAV) maintenance therapy. METHODS: In a 24-month phase III randomised-controlled trial, 115 patients over time received rituximab or azathioprine for AAV maintenance therapy. Mean changes of 36-item Short-form Health Survey (SF-36) and Health Assessment Questionnaire (HAQ) scores from baseline were analysed. RESULTS: Mean improvements of HAQ scores, from baseline to month 24 were significantly better for the rituximab (0.16 points lower) than the azathioprine group (p=0.038). As demonstrated by SF-36, study patients' baseline HRQOL was significantly impaired compared with age- and sex-matched US norms. At month 24, mean changes from baseline of SF-36 physical component score tended to be better for the rituximab group (+3.95 points, p=0.067) whereas mean changes from baseline of the SF-36 mental component score were significantly better for the azathioprine group (+4.23 points, p=0.041). CONCLUSIONS: Azathioprine-treated patients' for AAV maintenance therapy showed a decline in physical abilities when compared to RTX at M24 in the MAINRITSAN trial. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00748644

35. French-language version of the World Health Organization quality of life spirituality, religiousness and personal beliefs instrument

Author: Olfa Mandhouj, Henri-Jean Aubin, Delphine S. Courvoisier, Jean-François Etter, Association de santé mentale du 13ème arrondissement de Paris, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Social and Preventive Medicine, University of Geneva [Switzerland], Division of Clinical Epidemiology, Geneva University Hospital (HUG), Service d'addictologie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse, BMC, Ed., and Université de Genève = University of Geneva (UNIGE)
Subjects: Male, Psychometrics, Social connectedness, 050109 social psychology, 0302 clinical medicine, Social desirability bias, Social Desirability, Residence Characteristics, Surveys and Questionnaires, Spirituality, 030212 general & internal medicine, Language, 05 social sciences, General Medicine, Middle Aged, humanities, Religion, lcsh:R858-859.7, Educational Status, Female, France, Psychology, Social psychology, Clinical psychology, Adult, Quality of life, Religiousness, lcsh:Computer applications to medicine. Medical informatics, World Health Organization, Validity, 03 medical and health sciences, Interpersonal relationship, Quality of life (healthcare), Professional Role, Cronbach's alpha, Humans, 0501 psychology and cognitive sciences, Interpersonal Relations, Internet surveys, Internet, Research, Public Health, Environmental and Occupational Health, Construct validity, Reproducibility of Results, Health Surveys, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Linear Models, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Background A valid assessment of spirituality and religiousness is necessary for clinical and research purposes. We developed and assessed the validity of a French-language version of the World Health Organization Quality of Life Spirituality, Religiousness and Personal Beliefs Instrument (WHOQOL-SRPB). Methods The SRPB was translated into French according to the methods recommended by the WHOQOL group. An Internet survey was conducted in 561 people in 2010, with follow-up 2 weeks later (n = 231, 41%), to assess reliability, factor structure, social desirability bias and construct validity of this scale. Tests were performed based on item-response theory. Results A modal score of 1 (all answers=”not at all”) was observed for Faith (in 34% of participants), Connectedness (27%), and Spiritual Strength (14%). All scales had test-retest reliability coefficients ≥0.7. Cronbach’s alpha coefficients were high for all subscales (0.74 to 0.98) and very high (>0.9) for three subscales (Connectedness, Spiritual Strength and Faith). Scores of Faith, Connectedness, Spiritual Strength and Meaning of Life were higher for respondents with religious practice than for those who had no religious practice. No association was found between SRPB and age or sex. The Awe subscale had a low information function for all levels of the Awe latent trait and may benefit from inclusion of an additional item. Conclusions The French language version of the SRPB retained many properties of the original version. However, the SRPB could be improved by trimming redundant items. The strength of SRPB relies on its multinational development and validation, allowing for cross-cultural comparisons.
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36. Increased formation of VAMP-3-containing SNARE complexes in mast cells from VAMP-8 deficient cells. appetite.

Author: Tiwari N, Wang CC, Brochetta C, Scandiuzzi L, Hong W, and Blank U
Subjects: Animals, Bone Marrow Cells cytology, Bone Marrow Cells immunology, Mast Cells cytology, Mice, Mice, Knockout, Mast Cells immunology, Qb-SNARE Proteins metabolism, Qc-SNARE Proteins metabolism, R-SNARE Proteins metabolism, SNARE Proteins metabolism, Vesicle-Associated Membrane Protein 3 metabolism
Published: 2009
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