Search

Your search keyword '"Rheumatology, Clinical"' showing total 17 results
Start Over Author "Rheumatology, Clinical" Database OpenAIRE
17 results on '"Rheumatology, Clinical"'

1. Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers

Author

FinnGen Rheumatology Clinical Expe, Palomaki, Antti, Palotie, Aarno, Koskela, Jukka, Eklund, Kari K., Pirinen, Matti, Ripatti, Samuli, Laitinen, Tarja, Mars, Nina, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Complex Disease Genetics, HUS Helsinki and Uusimaa Hospital District, HUS Inflammation Center, Department of Medicine, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Department of Public Health, and Samuli Olli Ripatti / Principal Investigator

Subjects
rheumatoid arthritis, pulmonary fibrosis, PULMONARY-FIBROSIS, 3121 General medicine, internal medicine and other clinical medicine, respiratory system, genetic, behavioral disciplines and activities, respiratory tract diseases, polymorphism
Abstract

Objectives To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. Methods FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. Results Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. Conclusion Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.

Published
2021

2. Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers

Author

Palomäki, A. (Antti), FinnGen Rheumatology Clinical Expert Group, Palotie, A. (Aarno), Koskela, J. (Jukka), Eklund, K. K. (Kari K.), Pirinen, M. (Matti), FinnGen, Ripatti, S. (Samuli), Laitinen, T. (Tarja), and Mars, N. (Nina)

Abstract

Objectives: To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. Methods: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. Results: Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. Conclusion: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.

Published
2021

3. The Italian observational study on severe osteoporosis (ISSO): 24-month results on incidence of fractures and adherence to treatment

Author

Window, Trova@UniTO(opens in a. new, Export, Download | Add to List | More,, Rheumatology, Clinical, Experimental, Volume 34, Issue 2, The Italian observational study on severe osteoporosis: 24 month results on incidence of fractures, adherence to treatment Idolazzi, L. Abb, Maugeri, D. B, Monti, S. C, Massarotti, M. D, Osella, G. E, Barbagallo, M. F, Del Fiacco, R. G, Silvestri, S. G, Adami, S. H, Altomonte, L. I, Bardoscia, A. J, Bertoldo, F. K, Bevilacqua, M. L, Bianchi, G. M, Brancati, A. N, Cagnoni, C. O, Cantatore, F. P. P, Capone, A. Q, Costanzo, G. R, D'Avola, G. S, De Giorgi, G. T, Di Matteo, L. U, Di Munno, O. V, Filipponi, P. W, Frisina, N. X, Fusco, A. Y, Giannini, S. Z, Guiducci, S. Aa, Iolascon, G. Ab, Isaia, Giovanni Carlo, Lombardi, G. Ad, Malavolta, N. Ae, Marcocci, C. Af, Migliaccio, S. Ag, Migliore, A. Ah, Muratore, M. Ai, Nardi, A. Aj, Ortolani, S. Ak, Pasquali, R. Al, Petto, H. Am, Pietrogrande, L. An, Pola, E. Ao, Previti, B. Ap, Resmini, G. Aq, Rubinacci, A. Ar, Russo, E. As, Scillitani, A. At, Silveri, F. Au, Leali, P. T. Av, Trotta, F. Aw, Ulivieri, M. Ax, Verdoia, C. Ay, Versace, F. Az, Vinicola, V. Ba, Idolazzi, Luca, Maugeri, Domenico, Monti, Salvatore, Massarotti, Marco, Osella, Giangiacomo, Barbagallo, Mario, Del Fiacco, Romano, Silvestri, Sandra, Adami, S, Altomonte, L, Barbagallo, M, Bardoscia, A, delle Murge, C, Bertoldo, F, Bevilacqua, M, Bianchi, G, Brancati, A, Cagnoni, C, Cantatore, Fp, Capone, A, DI COSTANZO, Gennaro, D'Avola, G, De Giorgi, G, Di Matteo, L, Di Munno, O, Filipponi, P, Frisina, N, Fusco, A, Giannini, S, Guiducci, S, Iolascon, G, Isaia, G, Lombardi, G, Malavolta, N, Marcocci, C, Migliaccio, S, Migliore, A, Muratore, M, Nardi, A, Ortolani, S, Osella, G, Pasquali, R, Petto, H, Pietrogrande, L, Pola, E, Previti, B, Resmini, G, Rubinacci, A, Russo, Pina Elvira, Scillitani, A, Silveri, F, Leali, Pt, Trotta, F, Ulivieri, M, Verdoia, C, Versace, F, and Vinicola, V.

Subjects
Aged, 80 and over, Male, Spinal fracture, Incidence, Osteoporosi, Middle Aged, Parathyroid hormone, Spine, Medication Adherence, Fracture, Observational study, Osteoporosis therapy, Teriparatide, 80 and over, Settore MED/33 - Malattie Apparato Locomotore, Humans, Osteoporosis, Female, Prospective Studies, Aged, Osteoporotic Fractures
Abstract

Objective To estimate the proportion of patients with very severe osteoporosis (those covered by the reimbursement criteria of the Italian National Health Service) experiencing new vertebral and non-vertebral fragility fractures in the first 24 months of a new anti-osteoporosis treatment. Methods Prospective observational study in men and post-menopausal women (aged > 21 years) initiating anti-osteoporosis treatment for very severe osteoporosis. Eligibility was based on teriparatide (TPD) reimbursement criteria in Italy: Incident of vertebral or hip fracture during anti-resorptive treatment (minimum 1 year), or at least three prevalent severe vertebral fractures, or two prevalent severe vertebral fractures and a historical proximal hip fracture. Incidence of new clinical vertebral and non-vertebral fractures was documented by original x-rays and/or radiological reports, and a post-hoc analysis compared data from the TPD monotherapy population versus the total treated group. Results Overall, 767 patients (mean age 72.8 years, 90.7% women) were enrolled in the study, of whom 628, 538, 419 and 424 attended visits at 6, 12, 18 and 24 months, respectively. The most commonly prescribed therapy was TPD (single-agent; 64.5%), then bisphosphonates and other anti-resorptives (33.3%). A combination of different oral treatments was given to 22.5% of the patients. Overall treatment adherence at 24 months was 65.7%. In a post-hoc analysis, the overall incidence of new clinical vertebral and non-vertebral fractures in the total treated population was, respectively, 4.7% and 2.3% in the first 6 months; 1.8% and 1.6% in the 6-12 month period; 2.9% and 1.4% in the 12-18 month period; and 2.2% and 1.0% in the 18-24 month period. Conclusion In patients with very severe osteoporosis, the risk of new vertebral and non-vertebral fractures declined after the first 6 months and remained low throughout the study. Objective To estimate the proportion of patients with very severe osteoporosis (those covered by the reimbursement criteria of the Italian National Health Service) experiencing new vertebral and non-vertebral fragility fractures in the first 24 months of a new anti-osteoporosis treatment. Methods Prospective observational study in men and post-menopausal women (aged > 21 years) initiating anti-osteoporosis treatment for very severe osteoporosis. Eligibility was based on teriparatide (TPD) reimbursement criteria in Italy: Incident of vertebral or hip fracture during anti-resorptive treatment (minimum 1 year), or at least three prevalent severe vertebral fractures, or two prevalent severe vertebral fractures and a historical proximal hip fracture. Incidence of new clinical vertebral and non-vertebral fractures was documented by original x-rays and/or radiological reports, and a post-hoc analysis compared data from the TPD monotherapy population versus the total treated group. Results Overall, 767 patients (mean age 72.8 years, 90.7% women) were enrolled in the study, of whom 628, 538, 419 and 424 attended visits at 6, 12, 18 and 24 months, respectively. The most commonly prescribed therapy was TPD (single-agent; 64.5%), then bisphosphonates and other anti-resorptives (33.3%). A combination of different oral treatments was given to 22.5% of the patients. Overall treatment adherence at 24 months was 65.7%. In a post-hoc analysis, the overall incidence of new clinical vertebral and non-vertebral fractures in the total treated population was, respectively, 4.7% and 2.3% in the first 6 months; 1.8% and 1.6% in the 6-12 month period; 2.9% and 1.4% in the 12-18 month period; and 2.2% and 1.0% in the 18-24 month period. Conclusion In patients with very severe osteoporosis, the risk of new vertebral and non-vertebral fractures declined after the first 6 months and remained low throughout the study.

Published
2016

4. BOB.1 controls memory B-cell fate in the germinal center reaction

Author

Dominique Baeten, Lisa G. M. van Baarsen, Sophie Brouard, Maartje J. Levels, Tom O'Toole, Nataliya Yeremenko, Arjen Q. Bakker, Mikhail Krasavin, Cynthia M. Fehres, JF Semmelink, Iris C Blijdorp, Alexey Tomilin, Marieke E. Doorenspleet, Kristine Germar, Nathalie O. P. van Uden, Hergen Spits, Department of Rheumatology & Clinical Immunology [Amsterdam, the Netherlands] (Amsterdam UMC), University of Amsterdam [Amsterdam] (UvA)-Amsterdam Infection & Immunity Institute [Amsterdam, the Netherlands], Department of Experimental Immunology [Amsterdam, the Netherlands] (Amsterdam UMC), Amsterdam Rheumatology & Immunology Center - ARC [Amsterdam, the Netherlands] (Amsterdam UMC), Amsterdam Infection & Immunity Institute [Amsterdam, the Netherlands] (Amsterdam UMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), AIMM Therapeutics [Amsterdam, the Netherlands], Saint Petersburg State University [Saint Petersburg, Russian Federation], Institute of Cytology and Genetics, Russian Academy of Sciences [Moscow] (RAS), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Clinical Immunology and Rheumatology, Graduate School, AII - Inflammatory diseases, 01 Internal and external specialisms, Dermatology, Experimental Immunology, AGEM - Digestive immunity, Le Bihan, Sylvie, and Molecular cell biology and Immunology

Subjects
Memory B cell, 0301 basic medicine, T-Lymphocytes, Plasma Cells, Immunology, Naive B cell, Gene Expression, Receptors, Antigen, B-Cell, Plasma cell, Biology, medicine.disease_cause, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Autoimmune disease, medicine, Animals, Humans, Immunology and Allergy, BOB.1, Rheumatoid arthritis, B cell, Mice, Knockout, 030203 arthritis & rheumatology, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Germinal center, Immune dysregulation, BCL6, 030104 developmental biology, medicine.anatomical_structure, Trans-Activators, Lymph Nodes, Rheumatic Fever, Immunologic Memory, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; During T cell-dependent (TD) germinal center (GC) responses, naïve B cells are instructed to differentiate towards GC B cells (GCBC), high-affinity long-lived plasma cells (LLPC) or memory B cells (Bmem). Alterations in the B cell-fate choice could contribute to immune dysregulation leading to the loss of self-tolerance and the initiation of autoimmune disease. Here we show that mRNA levels of the transcription regulator BOB.1 are increased in the lymph node compartment of patients with rheumatoid arthritis (RA), a prototypical auto-immune disease caused by the loss of immunological tolerance. Investigating to what extent levels of BOB.1 impact B cells during TD immune responses we found that BOB.1 has a crucial role in determining the B cell-fate decision. High BOB.1 levels promote the generation of cells with phenotypic and functional characteristics of Bmem. Mechanistically, overexpression of BOB.1 drives ABF1 and suppresses BCL6, favouring Bmem over LLPC or recycling GCBC. Low levels of BOB.1 are sufficient for LLPC but not for Bmem differentiation. Our findings demonstrate a novel role for BOB.1 in B cells during TD GC responses and suggest that its dysregulation may contribute to the pathogenesis of RA by disturbing the B cell-fate determination.

Published
2019
Full Text
View/download PDF

5. Type 2 diabetes mellitus and osteoarthritis

Author

André Scheen, René Rizzoli, Roland Roth, Lucio C. Rovati, Marc C. Hochberg, Mila Vlaskovska, Elaine M. Dennison, Nicola Veronese, Daniel Uebelhart, Emmanuel Maheu, Jean-François Kaux, Gabriel Herrero-Beaumont, Olivier Bruyère, Jaime Branco, Roland Chapurlat, Cyrus Cooper, Nasser M. Al-Daghri, Jean-Yves Reginster, Gestionnaire, Hal Sorbonne Université, Italian National Research Council [Padova, Italy], MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, NIHR Musculoskeletal Biomedical Research Unit [Oxford, UK], University of Oxford, WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging [Liège, Belgium], Department of Public Health, Epidemiology and Health Economics [Liège, Belgium], Université de Liège-CHU Sart Tilman [Liege, Belgium], Chair for Biomarkers of Chronic Diseases [Riyadh, Kingdom of Saudi Arabia] (Biochemistry Department), Qassim University [Kingdom of Saudi Arabia]-College of Science [Riyadh, Kingdom of Saudi Arabia], Medical Care Clinical Center [Baltimore, MD, USA], VA Maryland Health Care System [Baltimore, MD, USA], Division of Rheumatology & Clinical Immunology [Baltimore, MD, USA] (Department of Medicine), University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Geriatric Research [Baltimore, MD, USA], Education and Clinical Center [Baltimore, MD, USA], Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Bone and Joint Research Unit [Madrid, Spain] (Department of Rheumatology), IIS‑Fundación Jiménez Diaz‑Autonoma University [Madrid, Spain], Department of Physical & Rehabilitation Medicine and Sports Traumatology, SPORTS-2 [Liège, Belgium], Université de Liège-Centre Hospitalier Universitaire de Liège (CHU-Liège)-FIFA Medical Centre of Excellence [Liège, Belgium], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Division of Bone Diseases [Geneva, Switzerland] (Faculty of Medicine), Hôpitaux Universitaires de Genève (HUG), Chiropractic, Naturopathy and Orthopaedics practice [Essen-Suedviertel, Germany], School of Medicine and Surgery [Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), Department of Clinical Research [Monza, Italy], Rottapharm Biotech [Monza, Italy], Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitatio [Crans-Montana, Switzerland] (Orthopaedics and Traumatology), Hôpital du Valais [Crans-Montana, Switzerland] (HVS)-Centre Hospitalier du Valais Romand [Crans-Montana, Switzerland] (CHVR), Department of Pharmacology [Sofia, Bulgaria] (Medical Faculty), Medical University-Sofia [Sofia, Bulgaria], Division of Diabetes, Nutrition and Metabolic Disorders [Liège, Belgium] (Department of Medicine), Clinical Pharmacology Unit [Liège, Belgium], The meeting was funded by the ESCEO, a Belgian not-for-profitorganization., UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), University of Oxford [Oxford], Centre Hospitalier Universitaire de Liège (CHU-Liège)-Université de Liège-FIFA Medical Centre of Excellence [Liège, Belgium], Università degli Studi di Milano [Milano] (UNIMI), Veronese, N., Cooper, C., Reginster, J.-Y., Hochberg, M., Branco, J., Bruyère, O., Chapurlat, R., Al-Daghri, N., Dennison, E., Herrero-Beaumont, G., Kaux, J.-F., Maheu, E., Rizzoli, R., Roth, R., Rovati, L.C., Uebelhart, D., Vlaskovska, M., and Scheen, A.

Subjects
medicine.medical_specialty, Evidence-based practice, type 2 diabetes mellitu, endocrine system diseases, Medicina, Osteoarthritis, Overweight, Pathophysiology, Article, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Rheumatology, Internal medicine, Type 2 diabetes mellitus, Medicine, Humans, 030212 general & internal medicine, Obesity, Risk factor, 030203 arthritis & rheumatology, ddc:616, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Institutional repository, Anesthesiology and Pain Medicine, Diabetes Mellitus, Type 2, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Disease Progression, osteoarthriti, medicine.symptom, Insulin Resistance, Safety, business
Abstract

Objectives: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. Methods: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. Results: T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. Conclusions: Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues., The meeting was funded by the ESCEO, a Belgian not-for-profit organization. The authors thank the Chair for Biomarkers of Chronic Diseases and the International Scientific Partnership Program (ISPP#0111) at King Saud University, Riyadh, Saudi Arabia for their support

Published
2019
Full Text
View/download PDF

6. Brief Report: Interleukin‐17 Blockade With Secukinumab in Peripheral Spondyloarthritis Impacts Synovial Immunopathology Without Compromising Systemic Immune Responses

Author

Nataliya Yeremenko, Inka A. Fluri, Talia E. Latuhihin, Henriëtte M. de Jong, Leonieke J J van Mens, S. Menegatti, Marleen G H van de Sande, Lars Rogge, Sijia Chen, Iris C Blijdorp, Dominique Baeten, Arno W R van Kuijk, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Institut Pasteur [Paris], Department of Rheumatology & Clinical Immunology [Amsterdam, the Netherlands] (Amsterdam UMC), Amsterdam Infection & Immunity Institute [Amsterdam, the Netherlands]-University of Amsterdam [Amsterdam] (UvA), Institut Pasteur [Paris] (IP), University of Amsterdam [Amsterdam] (UvA)-Amsterdam Infection & Immunity Institute [Amsterdam, the Netherlands], Clinical Immunology and Rheumatology, Graduate School, AII - Inflammatory diseases, 01 Internal and external specialisms, General Internal Medicine, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Synovial Membrane / drug effects, Severity of Illness Index, Spondylarthritis / immunology, 0302 clinical medicine, Immunopathology, Monoclonal, Immunology and Allergy, Synovial Membrane / immunology, Humanized, medicine.diagnostic_test, Spondylarthritis / drug therapy, Interleukin-17, Synovial Membrane, Antibodies, Monoclonal, Antirheumatic Agents / pharmacology, Middle Aged, 3. Good health, Cytokine, Treatment Outcome, Antirheumatic Agents, Erythrocyte sedimentation rate, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interleukin 17, Interleukin-17 / immunology, Adult, Monoclonal / pharmacology, Immunology, Antibodies, Monoclonal, Humanized, Antibodies, 03 medical and health sciences, Psoriatic arthritis, Immune system, Rheumatology, Spondylarthritis, medicine, Biomarkers / blood, Humans, Spondylarthritis / blood, 030203 arthritis & rheumatology, Ankylosing spondylitis, business.industry, medicine.disease, 030104 developmental biology, Secukinumab, business, Biomarkers
Abstract

International audience; Objective: Secukinumab (anti-interleukin-17A [anti-IL-17A]) is an effective therapy for ankylosing spondylitis and psoriatic arthritis, the prototypical forms of spondyloarthritis (SpA). We undertook this study to determine whether secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA as a model.Methods: Twenty patients with active peripheral SpA were included in a 12-week open-label trial with secukinumab (300 mg once weekly from baseline to week 4 and then every 4 weeks thereafter). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histologic and real-time quantitative polymerase chain reaction analysis of synovial biopsy samples before and after treatment.Results: All patients completed the 12-week study without severe adverse events (AEs) or severe treatment-related AEs. The efficacy end point, the number of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks, was achieved by 13 of the 20 patients, of whom 8 achieved an ACR50 response and 5 achieved an ACR70 response, with rapid and significant improvements in all clinical disease activity measures. Clinical improvement in joint counts was associated with a histologic decrease in synovial sublining macrophages (P = 0.028) and neutrophils (P = 0.004), both of which are sensitive synovial biomarkers of inflammatory response in peripheral SpA, as well as with decreased synovial expression of IL-17A messenger RNA (mRNA) (P = 0.010) but not of tumor necrosis factor mRNA. Systemically, secukinumab treatment decreased the C-reactive protein level and the erythrocyte sedimentation rate (both P < 0.01), and also decreased matrix metalloproteinase 3 production in the TruCulture system (P < 0.05). However, with the exception of IL-17A itself, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected.Conclusion: This mechanism-of-action study in peripheral SpA indicates that clinical improvement with secukinumab treatment is paralleled by immunomodulation of inflamed target tissues without compromising systemic immune responses.

Published
2018
Full Text
View/download PDF

7. A fine bioinformatical analysis of lymphocyte distribution predicts the diagnosis of primary Sjögren's syndrome among other systemic autoimmune diseases

Author

Simon, Quentin, Rouvière, Bénédicte, Martin, Tifenn, Le Lann, Lucas, Saraux, Alain, Devauchelle-Pensec, Valérie, Marañon, Concepción, Hernandez, Nievas Varela, Dufour, Aleksandra Maria, Chizzolini, Carlo, de Langhe, Ellen, Barbarroja, Nuria, Lopez-Pedrera, Chary, Gerl, Velia, Degroof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alarcón-Riquelme, Marta, Christophe, Jamin, Pers, Jacques-Olivier, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre for Genomics and Oncological Reearch (GENYO), University of Geneva [Switzerland], Immunology and Allergy, University Hospital and School of Medicine, University Hospitals Leuven [Leuven], Laboratorio de Investigaciones Biomedicas, Fundacion IMABIS. Hospital Virgen de la Victoria, IMIBIC Hospital Universitario Reina Sofia, University of Córdoba [Córdoba], Reina Sofia University Hospital, IMIBIC, University of Cordoba. Ciber Fisiopatologia Obesidad y Nutricion, Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], UCL, Université Catholique de Louvain - Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical & Experimental Medicine, Louvain, Belgique, SS/IREC/RUMA Cliniques Universitaires St Luc, Fondazione IRCCS Servizio Di Citometria, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

8. Comparative effectiveness of treatment with the first TNF antagonist in monotherapy, the first TNF antagonist plus one conventional synthetic disease-modifying antirheumatic drug, and the first TNF antagonist plus two or more conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis

Author

Rafael Caliz-Caliz, F. Navarro-Sarabia, Blanca Hernández-Cruz, Esther Márquez-Saavedra, [Hernández-Cruz,B, Navarro-Sarabia,F] Rheumatology Clinical Unit, Virgen de la Macarena University Hospital, Andalusian Health Service, Seville, Spain. [Márquez-Saavedra,E] Pharmaceutical Supplies and Services, Central Services, Reina Sofia University Hospital, Andalusian Health Service, Cordoba, Spain. [Caliz-Caliz,R] Rheumatologist, Head of Service., Virgen de las Nieves University Hospital, Andalusian Health Service, Granada, Spain., and This work was funding by a limited grant from the Andalucian Foundation of Rheumatology.

Subjects
Male, medicine.medical_treatment, Pharmacology, Gastroenterology, Chemicals and Drugs::Biological Factors [Medical Subject Headings], Arthritis, Rheumatoid, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Prednisone, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [Medical Subject Headings], 030212 general & internal medicine, Prospective Studies, Practice Patterns, Physicians', Prospective cohort study, Middle Aged, Antirheumatic Agents, Treatment Outcome, Antirreumáticos, Rheumatoid arthritis, csDMARDs, Toxicity, Female, TNF antagonist, medicine.drug, Research Article, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Artritis reumatoide, Factores biológicos, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic Agents [Medical Subject Headings], 03 medical and health sciences, Internal medicine, Diseases::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Rheumatoid [Medical Subject Headings], medicine, Humans, Disease-modifying antirheumatic drug, Glucocorticoides, Glucocorticoids, Aged, 030203 arthritis & rheumatology, business.industry, Tumor Necrosis Factor-alpha, medicine.disease, Rheumatology, Chemicals and Drugs::Complex Mixtures::Biological Products [Medical Subject Headings], Chemicals and Drugs::Polycyclic Compounds::Steroids::Pregnanes::Pregnadienes::Pregnadienediols::Prednisone [Medical Subject Headings], Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Adrenal Cortex Hormones::Glucocorticoids [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Concomitant, business, RA
Abstract

Journal Article; BACKGROUND Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus, they are treated with the first TNF antagonists in monotherapy. The aim of this study was to analyse the csDMARD and GC prescription patterns before and during treatment with the first TNF antagonist, and compare their effectiveness in three groups of patients. METHODS An observational, prospective, multicentre study in common clinical practice was designed. Treating rheumatologists recorded patient variables, including previous and concomitant csDMARDs and GCs in a database. The data were analysed using descriptive, inferential and multivariate statistics. RESULTS There were 1136 patients included; 21 % received the first TNF antagonist in monotherapy, 67 % received the first TNF antagonist plus one csDMARD, and 12 % the first TNF antagonist plus two or more csDMARDs. Most patients were female (73 %), RF+, and ACPA+, and had erosions; mean age was 53.2 (±13.0) years, and duration of disease was 9.1 (±7.6) years. They had high activity with DAS28 of 5.8 ± 1.1, and poor physical function with HAQ of 1.43 ± 0.63, and significant differences between groups in clinical variables and comorbidities; 94 % had received treatment with GCs, MTX, LFN, or SSZ at any time before the first TNF antagonist, 5 % (n = 52) had been treated with CLQ or HCLQ, and 1 % (n = 13) had received neither GCs nor csDMARDs. Before the first TNF antagonist, the drugs most commonly used were GCs (78 %), MTX (50 %), LFN (44 %), and SSZ (21 %). Concomitantly with the first TNF antagonist, 977 patients (85 %) were receiving GCs, MTX, LFN, or SSZ; 15 % (n = 173) received their first TNF antagonist without any concomitant GCs or csDMARDs, true monotherapy, and 6 % received their first TNF antagonist with GCs. The drug most commonly used at the time of first TNF antagonist initiation was MTX (58 %). All treatment groups had clinically and statistically significant improvements in DAS and HAQ scores. Effectiveness analysis (controlling for confounders) showed mean drug survival of 16.7, 20.1 and 11.7 months in each group, respectively (p

Published
2016

9. Overestimating the Role of Environment in Cancers

Author

Michael E. Hochberg, Oliver Kaltz, Leonard Nunney, Robert Noble, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Department of Biology [Riverside], University of California [Riverside] (UCR), University of California-University of California, Division of Rheumatology & Clinical Immunology, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pathology, [SDV]Life Sciences [q-bio], MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, RC0254, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, ComputingMilieux_MISCELLANEOUS, GE, business.industry, Genetic data, Cancer, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Tissue type, Cancer development, business, Cancer risk, Cancer Etiology
Abstract

In a recent article, Wu and colleagues (Nature 2016;529:43–47) review previous studies and present new estimates for the contribution of extrinsic factors to cancer development. The new estimates are generally close to 100%, even for bone and brain cancers that have no known associations with lifestyle and are typically not considered to be preventable. We find that the results of Wu and colleagues are incompatible with previous estimates derived from epidemiological and genetic data. We further argue that their methods are fundamentally flawed because they overlook important effects of tissue type on cancer risk. We therefore conclude that their results give a misleading view of cancer etiology and preventability. Cancer Prev Res; 9(10); 773–6. ©2016 AACR.

Published
2016
Full Text
View/download PDF

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

Author

Esmeralda Neves, Damiana Álvarez-Errico, Katja Kniesch, Marta E. Alarcón-Riquelme, Christophe Jamin, Aleksandra Maria Dufour, Nuria Barbarroja, Velia Gerl, Concepción Marañón, Jacques-Olivier Pers, Elena Trombetta, Tineke Cantaert, Julie Ducreux, Lucas Le Lann, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Chromatin and Disease Group (Cancer Epigenetics and Biology Programme (PEBC)), Laboratorio de Investigaciones Biomedicas, Fundacion IMABIS. Hospital Virgen de la Victoria, Laboratory of Tissue Homeostasis and Disease, Laborory of Tissue homeostasis and Disease, SS/IREC/RUMA Cliniques Universitaires St Luc, Institut d'ethnologie méditerranéenne, européenne et comparative (IDEMEC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Klinik Für Immunologie Und Rheumatologie, Klinik Fü Immunologie Und Rheumatologie, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Fondazione IRCCS Servizio Di Citometria, Centre for Genomics and Oncological Reearch (GENYO), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Michel, Geneviève

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Computer science, Immunology, Context (language use), Harmonization, computer.software_genre, Antibodies, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Surface marker, Immunology and Allergy, Humans, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Flow Cytometry, 3. Good health, Europe, 030104 developmental biology, Flow (mathematics), Calibration, [SDV.IMM]Life Sciences [q-bio]/Immunology, Data mining, computer, Standard operating procedure
Abstract

The innovative medicine initiative project called PRECISESADS will study 2.500 individuals affected by systemic autoimmune diseases (SADs) and controls. Among extensive OMICS approaches, multi-parameter flow cytometry analyses will be performed in eleven different centers. Therefore, the integration of all data in common bioinformatical and biostatistical investigations requires a fine mirroring of all instruments. We describe here the procedure elaborated to achieve this prerequisite. One flow cytometer chosen as reference instrument fixed the mean fluorescence intensities (MFIs) of 8 different fluorochrome-conjugated antibodies (Abs) using VersaComp Ab capture beads. The ten other centers adjusted their own PMT voltages to reach the same MFIs. Subsequently, all centers acquired Rainbow 8-peak beads data on a daily basis to follow the stability of their instrument overtime. One blood sample has been dispatched and concomitantly stained in all centers. Comparison of leukocytes frequencies and cell surface marker MFIs demonstrated the close sensitivity of all flow cytometers, allowing a multicenter analysis. The effective multi-center harmonization enables the constitution of a workable wide flow cytometry database for the identification of specific molecular signatures in individuals with SADs.

Published
2016

11. Multi-center harmonization of flow cytometers for multicolor analyses of a large cohort of patients in the context of the European IMI PROJECT 'PRECISESADS'

Author

Pers, Jacques-Olivier, Le Lann, Lucas, Marañón, Concepción, Barbarroja, Nuria, Alvarez-Errico, Damiana, Trombetta, Elena, Gerl, Velia, Zuber, Aleksandra, Cantaert, T, Neves, Esmeralda, Kniesch, K, Ducreux, Julie, Christophe, Jamin, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre for Genomics and Oncological Reearch (GENYO), Laboratorio de Investigaciones Biomedicas, Fundacion IMABIS. Hospital Virgen de la Victoria, Unitat de Bioquímica, Universitat de Barcelona (UB)-Facultat de Medicina, Fondazione IRCCS Servizio Di Citometria, Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CMU Department of Pathology and Immunology, Laboratory of Tissue Homeostasis and Disease, Laborory of Tissue homeostasis and Disease, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Klinik Für Immunologie Und Rheumatologie, Klinik Fü Immunologie Und Rheumatologie, SS/IREC/RUMA Cliniques Universitaires St Luc, and Michel, Geneviève

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

12. Harmonisation of eleven flow cytometers for multi-colour analyses of a large cohort of patients in the context of the European IMI project 'Precisesads'

Author

Pers, Jacques-Olivier, Le Lann, Lucas, Marañon, Concepcion, Barbarroja, Nuria, Alvarez, Damania, Trombetta, Elena, Gerl, Velia, Zuber, Aleksandra, Cantaert, T, Neves, Esmeralda, Kniesch, K, Ducreux, Julie, Christophe, Jamin, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, 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), Laboratorio de Investigaciones Biomedicas, Fundacion IMABIS. Hospital Virgen de la Victoria, PEBC Bellvitge Biomedical Research Institute, PEBC Bellitge Biomedical Research Institute, Fondazione IRCCS Servizio Di Citometria, Department of Rheumatology & Clinical Immunology, Hôpital Charité, Berlin, CMU Department of Pathology and Immunology, Laboratory of Tissue Homeostasis and Disease, Laborory of Tissue homeostasis and Disease, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Klinik Für Immunologie Und Rheumatologie, Klinik Fü Immunologie Und Rheumatologie, SS/IREC/RUMA Cliniques Universitaires St Luc, Université de Brest (UBO) - IFR148, 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), and Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

13. Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease

Author

Isabelle Cleynen, Emilie Vazeille, Daniel W. Hommes, Marta Artieda, Marie-Agnès Bringer, Daniel Lottaz, Rinse K. Weersma, Sylvia L.F. Pender, Jestinah M. Mahachie John, Tariq Ahmad, Atilla Tordai, Rebecca Morgan-Walsh, Gert De Hertogh, Ingrid Arijs, Hein W. Verspaget, Magdalena Szczypiorska, Peter L. Lakatos, Cisca Wijmenga, Frank Seibold, Paul Rutgeerts, Kirstie Parnell, Dominiek Staelens, Kristel Van Steen, Arlette Darfeuille-Michaud, Severine Vermeire, Stefan Müller, Department of Clinical and Experimental Medicine, Translational Research in GastroIntestinal Disorders, Université Catholique de Louvain = Catholic University of Louvain (UCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Progenika Biopharma, Dutch Initiative on Crohn and Colitis (ICC), Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), 1st Department of Medicine, Semmelweis University [Budapest], Department of Gastroenterolog, Spital Netz Bern, Peninsula Medical School, University of Exeter-Plymouth University, University Medical Center Groningen [Groningen] (UMCG), Montefiore Institute, Systems and Modeling Unit - GIGA-R, Bioinformatics and Modeling, Université de Liège, Faculty of medicine, Clinical and Experimental Sciences, University of Southampton, Department of Morphology and Molecular Pathology, University Hospital Gasthuisberg, Department of Clinical Research, University of Bern, Molecular Diagnostics, Hungarian National Blood Transfusion Service, Inflammatory Bowel Diseases Center, Division of Digestive Diseases, University of California [Los Angeles] (UCLA), University of California-University of California, Department of Genetics, Department of Rheumatology, Clinical Immunology and Allergology, University Hospital of Bern, CHU Clermont-Ferrand, European Community's Seventh Framework Programme (FP7) [200931], Centre Hospitalier Universitaire de Clermont-Ferrand, Association Francois Aupetit, Universiteit Leiden-Universiteit Leiden, University Hospital Gasthuisberg [Leuven], University of California (UC)-University of California (UC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Université Catholique de Louvain (UCL), and Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA)

Subjects
Candidate gene, Proteases, medicine.medical_specialty, Proteasome Endopeptidase Complex, Cell Survival, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Bacterial Adhesion, susceptibility, escherichia-coli strains, Pathogenesis, Immune system, Crohn Disease, Molecular genetics, nf-kappa-b, medicine, Escherichia coli, Humans, cancer, Intestinal Mucosa, Dystroglycans, negative regulator, Cells, Cultured, Genetic Association Studies, 2. Zero hunger, Tumor Suppressor Proteins, crohns-disease, ileal mucosa, Gastroenterology, NF-kappa B, Epithelial Cells, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, invasion, 3. Good health, Deubiquitinating Enzyme CYLD, Proteasome, Case-Control Studies, Immunology, APEH, cyld, Colitis, Ulcerative, I-kappa B Proteins, activation, Ubiquitin-Specific Proteases, Ubiquitin Thiolesterase, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Peptide Hydrolases
Abstract

Objective Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their inhibitors to maintain gut homeostasis. Unrestrained or excessive proteolysis can lead to pathological gastrointestinal conditions. The aim was to validate the identified protease IBD candidates from a previously performed systematic review through a genetic association study and functional follow-up. Design We performed a genetic association study in a large multicentre cohort of patients with Crohn's disease (CD) and UC from five European IBD referral centres in a total of 2320 CD patients, 2112 UC patients and 1796 healthy controls. Subsequently, we did an extensive functional assessment of the candidate genes to explore their causality in IBD pathogenesis. Results Ten single nucleotide polymorphisms (SNPs) in four genes were significantly associated with CD: CYLD, USP40, APEH and USP3. CYLD was the most significant gene with the intronically located rs12324931 the strongest associated SNP (p(FDR)=1.74e-17, OR=2.24 (1.83 to 2.74)). Five SNPs in four genes were significantly associated with UC: USP40, APEH, DAG1 and USP3. CYLD, as well as some of the other associated genes, is part of the ubiquitin proteasome system (UPS). We therefore determined if the IBD-associated adherent-invasive Escherichia coli (AIEC) can modulate the UPS functioning. Infection of intestinal epithelial cells with the AIEC LF82 reference strain modulated the UPS turnover by reducing poly-ubiquitin conjugate accumulation, increasing 26S proteasome activities and decreasing protein levels of the NF-kappa B regulator CYLD. This resulted in I kappa B-alpha degradation and NF-kappa B activation. This activity was very important for the pathogenicity of AIEC since decreased CYLD resulted in increased ability of AIEC LF82 to replicate intracellularly. Conclusions Our results reveal the UPS, and CYLD specifically, as an important contributor to IBD pathogenesis, which is favoured by both genetic and microbial factors.

Published
2014
Full Text
View/download PDF

14. Predictive immunomonitoring — The COST ENTIRE initiative

Author

Dusan Popadic, Carmen Scheibenbogen, Sarah Thunberg, Frank O. Nestle, Ola Winqvist, Emina Savic, Ignacio Anegon, Thomas Giese, Barbara Seliger, Federica Villanova, Françoise Mascart, Ann-Charlotte Wikström, Per Marits, M. Turina, Eva Martínez-Cáceres, Dominique Baeten, Ricardo Pujol-Borrell, Hermann Eibel, Institute of Microbiology and Immunology [Belgrade, Serbia] (School of Medicine), University of Belgrade [Belgrade], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Rheumatology & Clinical Immunology [Amsterdam, the Netherlands] (Amsterdam UMC), University of Amsterdam [Amsterdam] (UvA)-Amsterdam Infection & Immunity Institute [Amsterdam, the Netherlands], Centre for Chronic Immunodeficiency [Freiburg, Germany], University Medical Centre [Freiburg, Germany], Institute for Immunology [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg], Unit of Translational Immunology [Stockholm, Sweden] (Department of Medicine), Karolinska Institutet [Stockholm], Department of Cellular Biology, Physiology and Immunology [Barcelona, Spain], Universitat Autònoma de Barcelona (UAB), Laboratory of Vaccinology and Mucosal Immunity [Brussels, Belgium], Université libre de Bruxelles (ULB), St. John's Institute of Dermatology, King‘s College London, Institute of Medical Immunology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institute of Medical Immunology [Halle/Saale, Germany], Martin-Luther-University Halle-Wittenberg, Clinical immunology and transfusion medicine [Stockholm, Sweden], Karolinska University Hospital [Stockholm], Le Bihan, Sylvie, Autonomous University of Barcelona, Amsterdam institute for Infection and Immunity, and Clinical Immunology and Rheumatology

Subjects
medicine.medical_specialty, International Cooperation, Immunology, Health Promotion, Translational Research, Biomedical, 03 medical and health sciences, 0302 clinical medicine, Text mining, medicine, Humans, Organizational Objectives, Immunology and Allergy, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Inflammation, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Progressive multifocal leukoencephalopathy, Multiple sclerosis, medicine.disease, Europe, Immune System Diseases, 030220 oncology & carcinogenesis, Physical therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2013
Full Text
View/download PDF

15. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party

Author

Daikeler, T., Labopin, M., Gioia, M. di, Abinun, M., Alexander, T., Miniati, I., Gualandi, F., Fassas, A., Martin, T., Schwarze, C.P., Wulffraat, N., Buch, M., Sampol, A., Carreras, E., Dubois, B., Gruhn, B., Gungor, T., Pohlreich, D., Schuerwegh, A., Snarski, E., Snowden, J., Veys, P., Fasth, A., Lenhoff, S., Messina, C., Voswinkel, J., Badoglio, M., Henes, J., Launay, D., Tyndall, A., Gluckman, E., Farge, D., EBMT Autoimmune Disease Working, Department of Rheumatology, University Hospital Basel [Basel], Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Haematology Department, Careggi University Hospital, Newcastle General Hospital, Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biomedicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Haematology II, Ospedale San Martino, Neurology & Haematology, George Papanicolau Hospital, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Paediatric Haematology & Endocrinology, University Children's Hospital, University Medical Center, VU University Medical Center [Amsterdam], Section of Musculoskeletal Disease, University of Leeds, Hospital Universitari Son Espases, Department of Hematology, Hospital Clinic Barcelona, Department of Neurology, University Hospitals Leuven [Leuven], Department of Pediatrics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Division of Immunology/Hematology/BMT, Charles University Hospital, Leiden University Medical Center (LUMC), Department of Hematology & Oncology, Medical University of Warsaw - Poland, Department of Haematology & Department of Oncology, NHS & University of Sheffield, Great Ormond Street Hospital for Children [London] (GOSH), University of Gothenburg (GU), University Hospital Lund, Dipartimento di Pediatria, Cinica di Oncoematologia Pediatrica, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Hematology & Rheumatology, University Hospital Tübingen, Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinical Research Unit, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), EULAR Grant & Freiwillige Akademische Gesellschaft Basel, Università degli Studi di Firenze = University of Florence (UniFI), Universiteit Leiden-Universiteit Leiden, University of Sheffield [Sheffield], and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, stem-cell transplantation bone-marrow-transplantation hemolytic-anemia blood, medicine.medical_treatment, Hematopoietic stem cell transplantation, Biochemistry, Autoimmune thrombocytopenia, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Prednisone, immune system diseases, Risk Factors, hemic and lymphatic diseases, Child, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, 3. Good health, Europe, surgical procedures, operative, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Rituximab, Female, Autoimmune hemolytic anemia, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Autoimmune Diseases, 03 medical and health sciences, Young Adult, Antiphospholipid syndrome, Internal medicine, medicine, Humans, Immunologic Factors, Cyclophosphamide, Glucocorticoids, Retrospective Studies, Autoimmune disease, Lupus erythematosus, business.industry, Infant, Cell Biology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Multivariate Analysis, business, 030215 immunology
Abstract

To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34+ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.

Published
2011
Full Text
View/download PDF

16. The role of pain and functional impairment in the decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1909 patients. Report of the OARSI-OMERACT Task Force on total joint replacement

Author

Gossec, L., Paternotte, S., Maillefert, J.F., Combescure, C., Conaghan, P.G., Davis, A.M., Gunther, K.P., Hawker, G., Hochberg, M., Katz, J.N., Kloppenburg, M., Lim, K., Lohmander, L.S., Mahomed, N.N., March, L., Pavelka, K., Punzi, L., Roos, E.M., Sanchez-Riera, L., Singh, J.A., Suarez-Almazor, M.E., Dougados, M., OARSI-OMERACT Task Force Total Art, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), APHP, Rheumatology B Department, Service de Rhumatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Division of Clinical Epidemiology (DCE), Geneva University Hospital (HUG), Section of Musculoskeletal Diseasee, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Division of Health Care and Outcomes Research and Arthritis and Community, Research and Evaluation Unit, Toronto, Department of Orthopaedic Surgery, Université Catholique de Louvain (UCL), Division of Rheumatology, Department of Medicine, Women's College Hospital, University of Toronto, Division of Rheumatology & Clinical Immunology, Department of Orthopedic Surgery, Harvard Medical School [Boston] (HMS), Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, St Vincent's Hospital & Western Hospital, Melbourne, Department of Orthopaedics, Lund University, Lund, Sweden, Division of Orthopaedic Surgery, University of Toronto, Institute of Bone and Joint Research, The University of Sydney, Institute of Rheumatology, University Prague, Rheumatology Unit, Universita degli Studi di Padova, Institute of Sports and Clinical Biomechanics, University of Southern Denmark (SDU), Birmingham VA Medical Center, University of Alabama [Tuscaloosa] (UA), Section of Rheumatology, The University of Texas Health Science Center at Houston (UTHealth), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collier, Jean-Yves, Université Catholique de Louvain = Catholic University of Louvain (UCL), 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 - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Division of Clinical Epidemiology ( DCE ), Geneva University Hospital ( HUG ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Catholique de Louvain ( UCL ), Harvard Medical School, Boston, The University of Sydney [Sydney], UNIVERSITY OF SOUTHERN DENMARK, University of Alabama [Tuscaloosa] ( UA ), University of Texas at Houston [Houston] ( UTHealth ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]

Subjects
Male, SURGERY, medicine.medical_treatment, Arthroplasty, Replacement, Hip, Osteoarthritis, Severity of Illness Index, Osteoarthritis, Hip, RADIOGRAPHIC FEATURES, Disability Evaluation, 0302 clinical medicine, Medicine, Outpatient clinic, Orthopedics and Sports Medicine, 030212 general & internal medicine, PREDICTORS, Arthroplasty, Replacement, Knee, Pain Measurement/methods, Pain/diagnosis, Pain Measurement, ddc:616, ASSOCIATION, Osteoarthritis, Knee, Middle Aged, 3. Good health, PRIORITIZATION, TRIALS, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, Osteoarthritis, Hip/physiopathology/surgery, musculoskeletal diseases, medicine.medical_specialty, Joint replacement, Symptom, Decision Making, Biomedical Engineering, Pain, Article, 03 medical and health sciences, Rheumatology, Severity of illness, PHYSICAL-FUNCTION, Humans, Knee, ARTHROPLASTY, Rheumatology and Autoimmunity, Aged, 030203 arthritis & rheumatology, Hip surgery, Hip, Osteoarthritis, Knee/physiopathology/surgery, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Gold standard, [SCCO.NEUR] Cognitive science/Neuroscience, OUTCOME MEASURE, Knee Hip Osteoarthritis Joint replacement Surgery Symptom radiographic features physical-function outcome measure arthroplasty severity surgery trials prioritization association predictors, medicine.disease, Arthroplasty, SEVERITY, Cross-Sectional Studies, Orthopedic surgery, Physical therapy, Surgery, business
Abstract

Import JabRef | WosArea Orthopedics; Rheumatology; International audience; Objective: To assess the pain and functional disability levels corresponding to an indication for total joint replacement (TJR) in hip and knee osteoarthritis (OA). Methods: Design: International cross-sectional study in 10 countries. Patients: Consecutive outpatients with definite hip or knee OA attending an orthopaedic outpatient clinic. Gold standard measure for recommendation for TJR: Surgeon's decision that TJR is justified. Outcome measures: Pain (ICOAP: intermittent and constant osteoarthritis pain, 0-100) and functional impairment (HOOS-PS/KOOS-PS: Hip/Knee injury and Osteoarthritis Outcome Score Physical function Short-form, 0-100). Analyses: Comparison of patients with vs without surgeons' indication for TJR. Receiver Operating Characteristic (ROC) curve analyses and logistic regression were applied to determine cut points of pain and disability defining recommendation for TJR. Results: In all, 1909 patients were included (1130 knee/779 hip OA). Mean age was 66.4 [standard deviation (SD) 10.9] years, 58.1% were women; 628/1130 (55.6%) knee OA and 574/779 (73.7%) hip OA patients were recommended for TJR. Although patients recommended for TJR (yes vs no) had worse symptom levels [pain, 55.5 (95% confidence interval 54.2, 56.8) vs. 44.9 (43.2, 46.6), and functional impairment, 59.8 (58.7, 60.9) vs. 50.9 (49.3, 52.4), respectively, both P inf 0.0001]. there was substantial overlap in symptom levels between groups, even when adjusting for radiographic joint status. Thus, it was not possible to determine cut points for pain and function defining 'requirement for TJR'. Conclusion: Although symptom levels were higher in patients recommended for TJR, pain and functional disability alone did not discriminate between those who were and were not considered to need TJR by the orthopaedic surgeon. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Published
2011
Full Text
View/download PDF

17. Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications

Author

Karen M J Douglas, Dimitri P. Mikhailidis, George D. Kitas, Armen Yuri Gasparyan, Antonios Stavropoulos-Kalinoglou, Department of Rheumatology, Clinical Research Unit, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust (Teaching), Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital, University College London Medical School, University College London (UCL), Arthritis Research Campaign (ARC) Epidemiology Unit, and University of Manchester [Manchester]

Subjects
Blood Platelets, medicine.medical_specialty, P-selectin, Immunology, Arthritis, Inflammation, 030204 cardiovascular system & hematology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Cell-Derived Microparticles, Internal medicine, medicine, Immunology and Allergy, Humans, Platelet, Platelet activation, Rheumatoid arthritis, CD40 Antigens, Megakaryocytopoiesis, 030203 arthritis & rheumatology, business.industry, Thrombosis, medicine.disease, Cardiovascular risk, 3. Good health, P-Selectin, Cardiovascular Diseases, Antirheumatic Agents, Platelet function, medicine.symptom, business, Biomarkers
Abstract

International audience; Patients with rheumatoid arthritis (RA) are at high risk of cardiovascular events. Platelet biomarkers are involved in inflammation, atherosclerosis and thrombosis. Cardiovascular and RA-associated factors can alter the structure and function of platelets, starting from megakaryocytopoiesis. Reactive megakaryocytopoiesis increases circulating platelets count and triggers hyperactivity. Hyperactive platelets target synovial membranes with subsequent local rheumatoid inflammation. Hyperactive platelets interact with other cells, and target the vascular wall. Accumulating evidence suggests that disease modifying anti-rheumatic drugs (DMARD) decrease platelet activity.

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results