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

1. 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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2. 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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3. 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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4. 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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5. 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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6. 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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7. 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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8. 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

9. 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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10. 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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11. 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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12. 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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13. 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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14. 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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15. 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

16. 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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16 results on '"Immunopathologie rénale, récepteurs et inflammation"'

1. Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

2. Evaluation of the performances of ‘typical’ imaging abnormalities of axial spondyloarthritis: results of the cross-sectional ILOS-DESIR study

3. Extracellular fluid volume is associated with incident end-stage kidney disease and mortality in patients with chronic kidney disease

4. Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation

5. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides

6. The IgA1 immune complex–mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

7. 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

8. Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

9. 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

10. 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

11. Body mass index influences the response to infliximab in ankylosing spondylitis

12. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis

13. Breast milk immune complexes are potent inducers of oral tolerance in neonates and prevent asthma development

14. Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene

15. Rituximab versus azathioprine for ANCA-associated vasculitis maintenance therapy: Impact on global disability and health-related quality of life

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

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

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