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1. Relative Clinical Influence of Clinical, Laboratory, and Radiological Investigations in Early Arthritis on the Diagnosis of Rheumatoid Arthritis. Data from the French Early Arthritis Cohort ESPOIR

Author

Laure Gossec, Maxime Dougados, Bernard Combe, Alain Saraux, Christophe Combescure, Nathalie Rincheval, CHU Cochin [AP-HP], Division of Clinical Epidemiology ( DCE ), Geneva University Hospital ( HUG ), 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 ), Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Division of Clinical Epidemiology (DCE), Geneva University Hospital (HUG), 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), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP]

Subjects
Rheumatoid nodule, Arthritis, Severity of Illness Index, Arthritis, Rheumatoid, Cohort Studies, 0302 clinical medicine, MESH : Peptides, Cyclic, Immunopathology, MESH: Autoantibodies, Immunology and Allergy, 030212 general & internal medicine, MESH: Cohort Studies, MESH: Arthritis, Rheumatoid, Univariate analysis, MESH: Middle Aged, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, MESH : Adult, 3. Good health, Rheumatoid arthritis, Cohort, MESH : Severity of Illness Index, France, MESH : Sensitivity and Specificity, medicine.symptom, Adult, musculoskeletal diseases, medicine.medical_specialty, Immunology, MESH : Cohort Studies, Peptides, Cyclic, Sensitivity and Specificity, 03 medical and health sciences, Rheumatology, MESH: Severity of Illness Index, MESH : Autoantibodies, Synovitis, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH : France, MESH: Peptides, Cyclic, Autoantibodies, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, MESH: ROC Curve, medicine.disease, MESH: Sensitivity and Specificity, Surgery, Radiography, MESH: France, ROC Curve, MESH : Arthritis, Rheumatoid, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : ROC Curve
Abstract

Objective.To evaluate the relative level of influence of usual investigations in early arthritis on the diagnosis of rheumatoid arthritis (RA).Methods.Patients: those included in the ESPOIR early arthritis cohort, a national cohort of patients with grade ≥ 2 synovitis for > 6 weeks and < 6 months. The diagnostic properties of variables assessed at baseline were measured against the diagnosis of RA defined by American College of Rheumatology criteria (at any timepoint between inclusion and 12-month followup) and expert opinion. Various models, including (1) clinical data; (2) clinical + radiographic data (plain radiographs); (3) addition of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP); and (4) addition of HLA-DR typing, were assessed by comparing areas under the curves for ROC curves.Results.Of 731 patients studied, 372 (50.9%) satisfied criteria for RA at 1 year. In univariate analysis, sensitivity was highest for distal articular presentation (94.6%), presence of IgM RF (69.4%), pain on metatarso-phalangeal squeeze test (66.1%), and presence of anti-CCP (65.6%); whereas specificity was highest for nodules (100%), HLA typing: shared-epitope double dose (95.9%), radiographic erosions (86.5%), and anti-CCP antibodies (86.4%). The most efficient model included swollen joint count, morning stiffness, erosions, RF, and anti-CCP. Adding rheumatoid nodules, C-reactive protein, or HLA-DR information was not contributive.Conclusion.In addition to the clinical variables and radiographs, RF and/or anti-CCP are the single variables of interest that are contributive for the diagnosis of RA.

Published
2010
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2. Th2 Lymphoproliferative Disorder of Lat Y136F Mutant Mice Unfolds Independently of TCR-MHC Engagement and Is Insensitive to the Action of Foxp3+ Regulatory T Cells

Author

Céline Genton, Adrien Kissenpfennig, Michael Mingueneau, Hans Acha-Orbea, Marie Malissen, Sylvie Richelme, Ying Wang, Pierre Perrin, Stéphane Chevrier, Bruno Lucas, James P. DiSanto, Bernard Malissen, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry [Lausanne], Université de Lausanne (UNIL), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Biochemistry, Université de Lausanne ( UNIL ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
Adoptive cell transfer, MESH: Mice, Mutant Strains, MESH: Antigens, CD4, MESH : Green Fluorescent Proteins, T-Lymphocytes, Regulatory, MESH : Receptors, Antigen, T-Cell, MESH : T-Lymphocytes, Regulatory, Mice, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, MESH: Autoimmune Diseases, MESH : Cell Proliferation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Autoantibodies, Immunology and Allergy, MESH: Animals, MESH : Adaptor Proteins, Signal Transducing, 0303 health sciences, MESH : Lymphoproliferative Disorders, biology, FOXP3, Forkhead Transcription Factors, MESH: Receptors, Antigen, T-Cell, 3. Good health, MESH : Forkhead Transcription Factors, MESH : Histocompatibility Antigens Class II, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Membrane Proteins, MESH : Interleukin-7, Green Fluorescent Proteins, Immunology, Receptors, Antigen, T-Cell, Linker for Activation of T cells, Major histocompatibility complex, MESH: Phosphoproteins, Autoimmune Diseases, 03 medical and health sciences, MESH : Autoimmune Diseases, Th2 Cells, MESH: Green Fluorescent Proteins, Antigen, MESH: Forkhead Transcription Factors, MESH: Th2 Cells, MESH : Autoantibodies, MESH: Cell Proliferation, MESH : Mice, MHC class I, Animals, MESH: Mice, Adaptor Proteins, Signal Transducing, Autoantibodies, Cell Proliferation, MESH: Adaptor Proteins, Signal Transducing, 030304 developmental biology, Interleukin-7, MESH: T-Lymphocytes, Regulatory, T-cell receptor, Histocompatibility Antigens Class II, Autoantibody, Membrane Proteins, Phosphoproteins, Molecular biology, Lymphoproliferative Disorders, Mice, Mutant Strains, MESH: Interleukin-7, MESH : Th2 Cells, MESH : Mice, Mutant Strains, MESH : Membrane Proteins, MESH: Histocompatibility Antigens Class II, biology.protein, MESH : Antigens, CD4, MESH : Animals, MESH : Phosphoproteins, 030215 immunology
Abstract

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (LatY136F mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the LatY136F pathology constitutes a bona fide autoimmune disorder dependent on TCR specificity. Using adoptive transfer experiments, we demonstrated that the expansion and uncontrolled Th2-effector function of LatY136F CD4 cells are not triggered by an MHC class II-driven, autoreactive process. Using Foxp3EGFP reporter mice, we further showed that nonfunctional Foxp3+ regulatory T cells are present in LatY136F mice and that pathogenic LatY136F CD4 T cells were capable of escaping the control of infused wild-type Foxp3+ regulatory T cells. These results argue against a scenario where the LatY136F pathology is primarily due to a lack of functional Foxp3+ regulatory T cells and suggest that a defect intrinsic to LatY136F CD4 T cells leads to a state of TCR-independent hyperactivity. This abnormal status confers LatY136F CD4 T cells with the ability to trigger the production of Abs and of autoantibodies in a TCR-independent, quasi-mitogenic fashion. Therefore, despite the presence of autoantibodies causative of severe systemic disease, the pathological conditions observed in LatY136F mice unfold in an Ag-independent manner and thus do not qualify as a genuine autoimmune disorder.

Published
2008
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3. 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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4. Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification criteria: an analysis based on ESPOIR cohort data

Author

Fautrel, Bruno, Combe, B., Rincheval, Nathalie, Dougados, M., Saraux, Alain, Rhumatologie, Université Paris Diderot - Paris 7 (UPD7), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], 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), 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) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-IFR148, and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH : Aged, Logistic regression, Severity of Illness Index, MESH : Early Diagnosis, Arthritis, Rheumatoid, Cohort Studies, 0302 clinical medicine, MESH: Early Diagnosis, MESH : Peptides, Cyclic, Immunology and Allergy, MESH: Autoantibodies, MESH : Female, 030212 general & internal medicine, skin and connective tissue diseases, MESH: Cohort Studies, MESH: Aged, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Middle Aged, MESH : Adult, Connective tissue disease, MESH: Reproducibility of Results, MESH : Rheumatoid Factor, MESH: Young Adult, Rheumatoid arthritis, Cohort, Female, MESH : Severity of Illness Index, Adult, musculoskeletal diseases, medicine.medical_specialty, MESH: Rheumatoid Factor, Concordance, MESH : Male, Immunology, MESH : Young Adult, MESH : Cohort Studies, Peptides, Cyclic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, Rheumatology, Rheumatoid Factor, Internal medicine, MESH: Severity of Illness Index, MESH : Autoantibodies, medicine, Rheumatoid factor, Humans, MESH : Middle Aged, MESH: Peptides, Cyclic, Aged, Autoantibodies, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Reproducibility of Results, MESH : Humans, MESH: Biological Markers, Reproducibility of Results, MESH: Adult, medicine.disease, MESH: Male, MESH : Biological Markers, Early Diagnosis, MESH : Arthritis, Rheumatoid, Physical therapy, business, MESH: Female, Rheumatism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers
Abstract

BackgroundIn 2010, new classification criteria for rheumatoid arthritis (RA) were developed.ObjectiveTo assess agreement between 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria and the potential source of discordance, based on ESPOIR cohort data.Methods813 early arthritis patients were included in ESPOIR between 2002 and 2005. Between-criteria agreement was based on the κ coefficient. Discordance was explored by logistic regression.ResultsData for 811 patients were available, with their main characteristics as follows: women 77%, swollen joint count 7.2, tender joint count 8.4, disease activity score in 28 joints 5.2, rheumatoid factor 46%, anticitrullinated protein antibody (ACPA) 39%, structural damage 22%. At baseline, 579 (71.4%) patients met the 1987 ACR criteria and 641 (79.0%) the 2010 criteria. Agreement at baseline was discordant for 168 patients: 115 satisfied the 2010 criteria and 53 the 1987 criteria. Concordance between the two sets was fair, with a κ coefficient of 0.45 and 0.42 at baseline and year 2, respectively. The main sources of discordance were the number and symmetry of joint involvement, as well as ACPA status.Conclusion2010 ACR/EULAR criteria identified more patients with RA than did 1987 criteria. The 2010 criteria failed to identify RA patients with symmetrical seronegative arthritis and limited joint involvement.

Published
2012
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5. Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy

Author

Laurent Mesnard, Eric Rondeau, Christiane Mousson, G. Dautin, Pierre Ronco, Hanna Debiec, Chantal Jouanneau, L. Martin, 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 ), Urgences Néphrologiques & Transplantation Rénale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), EFS Bourgogne Franche-Comté ( EFS-BFC ), Etablissement Français du Sang (EFS), Service de néphrologie (CHU de Dijon), Agence de la Biomédecine, Fondation pour la Recherche Médicale and 'Association pour l'Utilisation du Rein Artificiel' (AURA). H.D. is the recipient of a 'Contrat d'Interface' from Assistance Publique-Hôpitaux de Paris., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Etablissement Français du Sang de Bourgogne Franche-Comté (site de Dijon) (EFS BFC (site de Dijon)), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), RONCO, Pierre, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)

Subjects
Male, MESH : Recurrence, MESH : DNA, Complementary, MESH: Glomerulonephritis, Membranous, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Glomerulonephritis, Membranous, 0302 clinical medicine, Recurrence, [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, Immunology and Allergy, Medicine, MESH: Autoantibodies, MESH : Fluorescent Antibody Technique, Direct, Pharmacology (medical), MESH : Female, MESH : Glomerulonephritis, Membranous, Receptor, MESH: Middle Aged, biology, MESH : Receptors, Phospholipase A2, Glomerulonephritis, Middle Aged, respiratory system, MESH : Adult, 3. Good health, Fluorescent Antibody Technique, Direct, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, lipids (amino acids, peptides, and proteins), De novo, Antibody, MESH: Fluorescent Antibody Technique, Direct, Adult, DNA, Complementary, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, MESH : Male, macromolecular substances, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, 03 medical and health sciences, recurrent, Antigen, Membranous nephropathy, stomatognathic system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Autoantibodies, MESH: Receptors, Phospholipase A2, Humans, MESH : Middle Aged, Direct fluorescent antibody, PLA2R1, Autoantibodies, Transplantation, MESH: Humans, business.industry, Receptors, Phospholipase A2, MESH : Humans, Autoantibody, membranous nephropathy, MESH: Adult, MESH: DNA, Complementary, medicine.disease, equipment and supplies, MESH: Male, MESH: Recurrence, Immunology, biology.protein, business, MESH: Female
Abstract

International audience; Recent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies.

Published
2011
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6. Hormonal replacement therapy may reduce the risk for RA in women with early arthritis who carry HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP: results from the ESPOIR cohort

Author

Maxime Dougados, Claire Bombardier, Bernard Combe, Alain Saraux, Carine Salliot, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institute for Work and Health (IWH), University of Toronto-St. Michael's Hospital-Institute of Medical Sciences, 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), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Institute for Work and Health ( IWH ), 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 ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]

Subjects
[SDV]Life Sciences [q-bio], Arthritis, Severity of Illness Index, Arthritis, Rheumatoid, 0302 clinical medicine, MESH : Peptides, Cyclic, immune system diseases, MESH: Autoantibodies, Immunology and Allergy, MESH : Female, skin and connective tissue diseases, HLA-DRB1, MESH: HLA-DRB1 Chains, MESH: Arthritis, Rheumatoid, 0303 health sciences, MESH : Estrogen Replacement Therapy, MESH: Middle Aged, Estrogen Replacement Therapy, MESH: Genetic Predisposition to Disease, MESH : Adult, Middle Aged, 3. Good health, Menopause, MESH: Young Adult, Transgender hormone therapy, Rheumatoid arthritis, Cohort, Disease Progression, MESH : Severity of Illness Index, MESH: Disease Progression, Female, musculoskeletal diseases, Adult, medicine.medical_specialty, Immunology, MESH : Young Adult, Peptides, Cyclic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, MESH : HLA-DR Antigens, Rheumatology, MESH : Autoantibodies, MESH: Severity of Illness Index, Internal medicine, medicine, Humans, MESH : Middle Aged, Genetic Predisposition to Disease, Risk factor, MESH: Peptides, Cyclic, 030304 developmental biology, Autoantibodies, MESH : HLA-DRB1 Chains, 030203 arthritis & rheumatology, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH: Adult, MESH : Disease Progression, HLA-DR Antigens, MESH: HLA-DR Antigens, medicine.disease, MESH: Estrogen Replacement Therapy, MESH : Arthritis, Rheumatoid, MESH : Genetic Predisposition to Disease, business, MESH: Female, HLA-DRB1 Chains
Abstract

International audience; OBJECTIVE: To assess the effect of reproductive factors, especially hormone replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of rheumatoid arthritis (RA) and the presence of anti-cyclic citrullinated peptide (CCP) antibodies in women included in the ESPOIR cohort (early arthritis cohort). METHODS: 568 patients were included in the analyses, which were performed using logistic regression. RESULTS: HRT reduced the risk of RA due to the HLA-DRB1 *01 and/or *04 alleles from OR 1.88 (95% CI 1.32 to 2.68, p

Published
2009
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