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1. Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases

Author: Alice Tison, Soizic Garaud, Laurent Chiche, Divi Cornec, and Marie Kostine
Subjects: Biological Products, Rheumatology, Antirheumatic Agents, Neoplasms, Humans, Symptom Flare Up, Immune Checkpoint Inhibitors, Immunosuppressive Agents, Autoimmune Diseases, Retrospective Studies
Abstract: Immune-checkpoint inhibitors (ICIs) have dramatically changed the management of advanced cancers. Designed to enhance the antitumour immune response, they can also cause off-target immune-related adverse events (irAEs), which are sometimes severe. Although the efficacy of ICIs suggests that they could have wide-ranging benefits, clinical trials of the drugs have so far excluded patients with pre-existing autoimmune disease. However, evidence is accumulating with regard to the use of ICIs in this 'at-risk' population, with retrospective data suggesting that they have an acceptable safety profile, but that there is a risk of disease flare or other irAE occurrence. The management of immunosuppressive drugs at ICI initiation in patients with autoimmune disease (or later in instances of disease flare or irAE) remains a question of particular interest in clinical practice, in which there is always a search for the balance between protecting against autoimmunity and ensuring a good tumour response. Although temporary use of immunosuppressants seems safe, prolonged use or use at ICI initiation might hamper the antitumour immune response, prompting clinicians to use the minimal efficient immunosuppressive regimen. However, a new paradigm is emerging, in which inhibitors of TNF or IL-6 could have synergistic effects with ICIs on tumour response, while also preventing severe irAEs. If confirmed, this 'decoupling' effect on toxicity and efficacy could change therapeutic practice in this field. Knowledge of the current use of ICIs in patients with pre-existing autoimmune disease, particularly with regard to the use of immunosuppressive drugs and/or biologic DMARDs, can help to guide clinical practice.
Published: 2022

2. Comparison of halo and compression signs assessed by a high frequency ultrasound probe for the diagnosis of Giant Cell Arteritis

Author: Steve Raoul Noumegni, Sandrine Jousse-Joulin, Clément Hoffmann, Divi Cornec, Valérie Devauchelle-Pensec, Alain Saraux, and Luc Bressollette
Subjects: Male, Cross-Sectional Studies, Giant Cell Arteritis, Internal Medicine, Humans, Female, Radiology, Nuclear Medicine and imaging, General Medicine, Ultrasonography, Doppler, Color, Sensitivity and Specificity, Aged, Temporal Arteries
Abstract: To evaluate the diagnosis performances of halo and compression signs alone and combined, assessed by a high frequency 22-MHz probe, and test their agreement in giant cell arteritis (GCA).In this cross-sectional study on patients suspected with GCA, halo sign was defined as hypo or iso-echogenic circumferential aspect of the vessel wall in transverse or longitudinal view; and compression sign was defined as visibility of the vessel wall upon transducer-imposed compression of the artery. Agreement of the two signs was tested using the Cohen's kappa statistic.A total of 80 patients (50% women) were included with a mean age of 74.4 years. Twenty participants (25%) were ultimately treated for GCA. Halo and compression signs have respective prevalences of 35% and 48%, with respective sensitivity and specificity of 80% and 80% for the halo sign; and 85% and 65% for the compression sign. The kappa coefficient for the global agreement of the two signs was 0.67 (95% confident interval: 0.54-0.85). Combination of the two signs give a sensitivity of 80% and a specificity of 81.7%.Halo and compression signs assessed by a high frequency probe, show a good level of agreement for the diagnosis of GCA and improve ultrasound specificity when combined together.
Published: 2022

3. Obinutuzumab as treatment for ANCA-associated vasculitis

Author: Naomi A Amudala, Sara Boukhlal, Brittany Sheridan, Carol A Langford, Abdallah Geara, Peter A Merkel, and Divi Cornec
Subjects: Male, Remission Induction, Granulomatosis with Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Monoclonal, Humanized, Antibodies, Antineutrophil Cytoplasmic, Treatment Outcome, Rheumatology, immune system diseases, Humans, Female, Pharmacology (medical), Prospective Studies, Rituximab
Abstract: Objectives Rituximab is a standard of care therapy for patients with ANCA-associated vasculitis. When rituximab is contraindicated, or in the case of refractory disease, other treatments are needed. Obinutuzumab is another anti-CD20 antibody for the treatment of haematological malignancies that may induce a deeper B cell depletion compared with rituximab. This article reviews three cases of patients with ANCA-associated vasculitis who were treated with obinutuzumab due to their history of anaphylactic reactions to rituximab. Methods Case series of three patients with ANCA-associated vasculitis treated with obinutuzumab. Results One female patient with microscopic polyangiitis and two male patients with granulomatosis with polyangiitis received obinutuzumab. The treatment was well-tolerated in all patients despite previous anaphylactic reaction to rituximab. Treatment with obinutuzumab was effective in (i) inducing disease remission, (ii) inducing total B cell depletion, and (iii) resulting in undetectable serum titres of ANCA. All three patients were re-treated with obinutuzumab for maintenance of remission. Conclusion Obinutuzumab appears to be a safe and efficacious therapy for patients with ANCA-associated vasculitis who have had refractory disease or a history of anaphylaxis to rituximab. Prospective studies comparing rituximab to obinutuzumab in ANCA-associated vasculitis patients are warranted.
Published: 2021

4. Health Care Utilization in Systemic Lupus Erythematosus in the Community: The Lupus Midwest Network

Author: Baptiste Chevet, Gabriel Figueroa-Parra, Maria O. Valenzuela-Almada, Mehmet Hocaoglu, Sebastian Vallejo, Shirley-Ann Osei-Onomah, Rachel E. Giblon, Jesse Y. Dabit, Alanna M. Chamberlain, Divi Cornec, Kurt J. Greenlund, Kamil E. Barbour, Cynthia S. Crowson, and Alí Duarte-García
Subjects: Male, Cohort Studies, Hospitalization, Rheumatology, Humans, Lupus Erythematosus, Systemic, Female, Middle Aged, Patient Acceptance of Health Care, United States, Retrospective Studies
Abstract: The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population.This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995-2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups.Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05-3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups.Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.
Published: 2022

5. Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial

Author: Valérie Devauchelle-Pensec, Guillermo Carvajal-Alegria, Emmanuelle Dernis, Christophe Richez, Marie-Elise Truchetet, Daniel Wendling, Eric Toussirot, Aleth Perdriger, Jacques-Eric Gottenberg, Renaud Felten, Bruno Jean Fautrel, Laurent Chiche, Pascal Hilliquin, Catherine Le Henaff, Benjamin Dervieux, Guillaume Direz, Isabelle Chary-Valckenaere, Divi Cornec, Dewi Guellec, Thierry Marhadour, Emmanuel Nowak, and Alain Saraux
Subjects: Male, Drug Tapering, Interleukin-6, Giant Cell Arteritis, Anti-Inflammatory Agents, Administration, Oral, General Medicine, Antibodies, Monoclonal, Humanized, C-Reactive Protein, Double-Blind Method, Polymyalgia Rheumatica, Humans, Prednisone, Administration, Intravenous, Female, Glucocorticoids, Aged
Abstract: ImportanceFew treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica.ObjectiveTo compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica.Design, Setting, and ParticipantsThis double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day.InterventionsPatients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone.Main Outcomes and MeasuresThe primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone.ResultsOf the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P P P Conclusions and RelevanceAmong patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms.Trial RegistrationClinicalTrials.gov Identifier: NCT02908217
Published: 2022

6. Abnormal B cell glycosylation in autoimmunity: A new potential treatment strategy

Author: Marie, Morel, Pierre, Pochard, Wiam, Echchih, Maryvonne, Dueymes, Cristina, Bagacean, Sandrine, Jousse-Joulin, Valérie, Devauchelle-Pensec, Divi, Cornec, Christophe, Jamin, Jacques-Olivier, Pers, and Anne, Bordron
Subjects: B-Lymphocytes, Glycosylation, Immunology, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Autoimmunity, Autoantibodies, Autoimmune Diseases
Abstract: Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are two autoimmune diseases characterised by the production of pathogenic autoreactive antibodies. Their aetiology is poorly understood. Nevertheless, they have been shown to involve several factors, such as infections and epigenetic mechanisms. They also likely involve a physiological process known as glycosylation. Both SLE T cell markers and pSS-associated autoantibodies exhibit abnormal glycosylation. Such dysregulation suggests that defective glycosylation may also occur in B cells, thereby modifying their behaviour and reactivity. This study aimed to investigate B cell subset glycosylation in SLE, pSS and healthy donors and to extend the glycan profile to serum proteins and immunoglobulins. We used optimised lectin-based tests to demonstrate specific glycosylation profiles on B cell subsets that were specifically altered in both diseases. Compared to the healthy donor B cells, the SLE B cells exhibited hypofucosylation, whereas only the pSS B cells exhibited hyposialylation. Additionally, the SLE B lymphocytes had more galactose linked to N-acetylglucosamine or N-acetylgalactosamine (Gal-GlcNAc/Gal-GalNAc) residues on their cell surface markers. Interestingly, some similar alterations were observed in serum proteins, including immunoglobulins. These findings indicate that any perturbation of the natural glycosylation process in B cells could result in the development of pathogenic autoantibodies. The B cell glycoprofile can be established as a preferred biomarker for characterising pathologies and adapted therapeutics can be used for patients if there is a correlation between the extent of these alterations and the severity of the autoimmune diseases.
Published: 2022

7. A Proinflammatory Cytokine Network Profile in Th1/Type 1 Effector B Cells Delineates a Common Group of Patients in Four Systemic Autoimmune Diseases

Author: Laëtitia Le Pottier, Maria Orietta Borghi, Jacques-Olivier Pers, Lucas Le Lann, Divi Cornec, Quentin Simon, Bénédicte Rouvière, Sophie Hillion, Christophe Jamin, Eléonore Bettachioli, Marta E. Alarcón-Riquelme, Alexis Grasseau, Yves Renaudineau, Rocio Aguilar-Quesada, and Marina Boudigou
Subjects: Adult, Male, Naive T cell, medicine.medical_treatment, T cell, Immunology, B-Lymphocyte Subsets, Autoimmune Diseases, Proinflammatory cytokine, Arthritis, Rheumatoid, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Immune system, Rheumatology, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Medicine, CXCL10, Prospective Studies, B cell, Autoantibodies, Cell Proliferation, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, Scleroderma, Systemic, Interleukin-6, business.industry, Autoantibody, Cell Differentiation, Receptor Cross-Talk, Middle Aged, Th1 Cells, Coculture Techniques, 3. Good health, Chemokine CXCL10, Cross-Sectional Studies, Sjogren's Syndrome, Cytokine, medicine.anatomical_structure, Cellular Microenvironment, Cytokines, Interleukin-2, Female, business, Biomarkers
Abstract: OBJECTIVE The effector T cell and B cell cytokine networks have been implicated in the pathogenesis of systemic autoimmune diseases, but the association of these cytokine networks with the heterogeneity of clinical manifestations and immune profiles has not been carefully examined. This study was undertaken to examine whether cytokine profiles can delineate distinct groups of patients in 4 systemic autoimmune diseases (systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and systemic sclerosis). METHODS A total of 179 patients and 48 healthy volunteers were enrolled in the multicenter cross-sectional PRECISE Systemic Autoimmune Diseases (PRECISESADS) study. Multi-low-dimensional omics data (cytokines, autoantibodies, circulating immune cells) were examined. Coculture experiments were performed to test the impact of the cytokine microenvironment on T cell/B cell cross-talk. RESULTS A proinflammatory cytokine profile defined by high levels of CXCL10, interleukin-6 (IL-6), IL-2, and tumor necrosis factor characterized a distinct group of patients in the 4 systemic autoimmune diseases. In each disease, this proinflammatory cluster was associated with a specific circulating immune cell signature, more severe disease, and higher levels of autoantibodies, suggesting an uncontrolled proinflammatory Th1 immune response. We observed in vitro that B cells reinforce Th1 differentiation and naive T cell proliferation, leading to the induction of type 1 effector B cells and IgG production. This process was associated with an increase in CXCL10, IL-6, IL-2, and interferon-γ production. CONCLUSION This composite analysis brings new insights into human B cell functional heterogeneity based on T cell/B cell cross-talk, and proposes a better stratification of patients with systemic autoimmune diseases, suggesting that combined biomarkers would be of great value for the design of personalized treatments.
Published: 2021

8. The diversity of the plasmablast signature across species and experimental conditions: A meta‐analysis

Author: Olivier Mignen, Sophie Hillion, Marina Boudigou, Magalie Michée-Cospolite, Laëtitia Le Pottier, Jacques-Olivier Pers, Christophe Jamin, Alexis Grasseau, Divi Cornec, Céline Delaloy, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-18-CE15-0002,CascadingPCdiff,Signalisations B et engagement précoce vers la différenciation plasmocytaire(2018)
Subjects: Genetically modified mouse, B-cell differentiation, [SDV]Life Sciences [q-bio], Plasma Cells, Immunology, Mice, Transgenic, Computational biology, Biology, Plasma cell, Transcriptome, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Immunology and Allergy, Antibody-Producing Cells, Gene, Transcription factor, Glycoproteins, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, Whole Genome Sequencing, Sequence Analysis, RNA, PAX5 Transcription Factor, RNA, Cell Differentiation, Original Articles, Antigens, CD20, meta-analysis, medicine.anatomical_structure, plasmablast, PAX5, Positive Regulatory Domain I-Binding Factor 1, IRF8, transcriptome, 030215 immunology
Abstract: International audience; Antibody-secreting cells (ASC) are divided into two principal subsets, including the long-lived plasma cell (PC) subset residing in the bone marrow and the short-lived subset, also called plasmablast (PB). PB are described as a proliferating subset circulating through the blood and ending its differentiation in tissues. Due to their inherent heterogeneity, the molecular signature of PB is not fully established. The purpose of this study was to decipher a specific PB signature in humans and mice through a comprehensive meta-analysis of different data sets exploring the PB differentiation in both species and across different experimental conditions. The present study used recent analyses using whole RNA sequencing in prdm1-GFP transgenic mice to define a reliable and accurate PB signature. Next, we performed similar analysis using current data sets obtained from human PB and PC. The PB-specific signature is composed of 155 and 113 genes in mouse and human being, respectively. Although only nine genes are shared between the human and mice PB signature, the loss of B-cell identity such as the down-regulation of PAX5, MS4A1, (CD20) CD22 and IL-4R is a conserved feature across species and across the different experimental conditions. Additionally, we observed that the IRF8 and IRF4 transcription factors have a specific dynamic range of expression in human PB. We thus demonstrated that IRF4/IRF8 intranuclear staining was useful to define PB in vivo and in vitro and able to discriminate between atypical PB populations and transient states.
Published: 2021

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

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

10. Eosinophilic granulomatosis with polyangiitis: the multifaceted spectrum of clinical manifestations at different stages of the disease

Author: Matthieu Groh, Sara Boukhlal, Divi Cornec, and Alvise Berti
Subjects: 0301 basic medicine, medicine.medical_specialty, Immunology, Churg-Strauss Syndrome, Antibodies, Monoclonal, Humanized, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Eosinophilia, Eosinophilic, Humans, Immunology and Allergy, Medicine, Asthma, 030203 arthritis & rheumatology, business.industry, medicine.disease, Dermatology, Treatment Outcome, 030104 developmental biology, Disease Progression, Interleukin-5, medicine.symptom, business, Granulomatosis with polyangiitis, Vasculitis, Mepolizumab, Scleritis, medicine.drug, Systemic vasculitis
Abstract: Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) usually occurs in patients with late-onset asthma and sustained peripheral blood eosinophilia and classically presents with a clinical multifaceted spectrum of manifestations, which may vary at the different stages of the natural history of the disease.Areas covered: We reviewed EGPA clinical presentation, focusing on clinical manifestations at three different phases of the disease: 1/before the development of overt vasculitis, 2/at vasculitis diagnosis and 3/during the long-term follow-up. An update on current classification criteria and recent therapeutic advances has been provided as well.Expert opinion: Asthma, chronic rhinosinusitis and blood eosinophilia could anticipate the overt vasculitis for years. An atopic background may be present in a subset of patients (25-30%), while ANCA presence varies between 10 and 40%. Systemic vasculitis rapidly occurs and clinical features demonstrating vasculitis processes (neuropathy, purpura, scleritis, alveolar hemorrhage and glomerulonephritis) develop along with systemic symptoms (50%). After vasculitis resolution, asthma remains severe in up to 50% of patients and incidence of isolated-asthma and rhinosinus exacerbations remains constantly high. Different sets of classification criteria have been published so far, and DCVAS diagnostic criteria will be presented soon. Interleukin-5 blockers seem to be promising to control the disease and to spare corticosteroids.
Published: 2020

11. Weight of Salivary-Gland Ultrasonography compared to Other items of the 2016 ACR/EULAR Classification Criteria for Primary Sjögren's Syndrome

Author: Caroline H. Shiboski, Daniel Hammenfors, Sandrine Jousse-Joulin, Valérie Devauchelle-Pensec, Divi Cornec, Chiara Baldini, Manuel Ramos-Casals, Alan N. Baer, Tatsufumi Nakamura, Malin V. Jonsson, Pilar Brito-Zerón, Emmanuel Nowak, Wan-Fai Ng, Hideki Nakamura, Raphaèle Seror, Benjamin A Fisher, Alain Saraux, Hendrika Bootsma, Florence Gatineau, Astrid Rasmussen, S. De Vita, Simon J. Bowman, Xavier Mariette, Vera Milic, Arjan Vissink, Thomas Dörner, Francesca Barone, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique (CIC - Brest), Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Johns Hopkins University School of Medicine [Baltimore], Department of Rheumatology, University Hospital Birmingham, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), H. CIMA-Sanitas, Barcelona, Medical Centre for Rheumatology, Berlin, Department of Medical Area, University Hospital Santa Maria della Misericordia, Udine, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Haukeland University Hospital, University of Bergen (UiB), Department of Clinical Science and Department of Rheumatology, Bergen, Institute of Clinical Dentistry [Bergen, Norway], Department of Paediatric Rheumatology, Hôpital de Bicêtre, APHP, National Reference Centre for Auto-inflammatory Diseases, University of Paris Sud, CHU de Bicêtre, University of Belgrade [Belgrade], Department of Immunology and Rheumatology, Nagasaki, Japan, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Oklahoma Medical Research Foundation, Medical Research Foundation, Departments of Orofacial Sciences and Pediatrics, University of California, Department of Radiology and Cancer Biology, Nagasaki, Department of Oral & Maxillofacial Surgery & Maxillofacial Prosthetics, University Medical Center Groningen and University of Groningen, Translational Immunology Groningen (TRIGR), Personalized Healthcare Technology (PHT), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 0301 basic medicine, musculoskeletal diseases, medicine.medical_specialty, diagnosis, Primary Sjögren’s syndrome, 030204 cardiovascular system & hematology, Salivary Glands, 03 medical and health sciences, Ultralyd / Ultrasound, 0302 clinical medicine, Internal medicine, Internal Medicine, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Ultrasonography, business.industry, classification criteria, salivary glands, ultrasonography, Algorithms, Sjogren's Syndrome, Medisinske fag: 700::Klinisk medisinske fag: 750::Reumatologi: 759 [VDP], stomatognathic diseases, 030104 developmental biology, Midical sciences: 700::Clinical medical sciences: 750::Rheumatology: 759 [VDP], Expert opinion, Weighted score, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Sjogren s, business
Abstract: Objective: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren’s syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. Methods: A secure web‐based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. Results: A criteria‐based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti‐SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer’s test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. Conclusion: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria. acceptedVersion
Published: 2020

12. Development and preliminary validation of the Sjögren’s Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren’s syndrome

Author: Raphaele, Seror, Gabriel, Baron, Marine, Camus, Divi, Cornec, Elodie, Perrodeau, Simon J, Bowman, Michele, Bombardieri, Hendrika, Bootsma, Jacques-Eric, Gottenberg, Benjamin, Fisher, Wolfgang, Hueber, Joel A, van Roon, Valérie, Devauchelle-Pensec, Peter, Gergely, Xavier, Mariette, Raphael, Porcher, Marie, Wahren-Herlenius, Piatrova, Alena, NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID, Translational Immunology Groningen (TRIGR), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), University Hospitals Birmingham [Birmingham, Royaume-Uni], University of Birmingham [Birmingham], Queen Mary University of London (QMUL), University of Groningen [Groningen], CHU Strasbourg, Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Novartis Pharma AG, Utrecht University [Utrecht], Novartis Institutes for BioMedical Research (NIBR), NECESSITY WP5- STAR development working group: Suzanne Arends, Francesca Barone, Albin Björk, Coralie Bouillot, Guillermo Carvajal Alegria, Wen-Hung Chen, Kenneth Clark, Konstantina Delli, Liseth de Wolff, Jennifer Evans, Stéphanie Galtier, Saviana Gandolfo, Mickael Guedj, Dewi Guellec, Safae Hamkour, Dominik Hartl, Malin V Jonsson, Roland Jonsson, Frans G M Kroese, Aike Albert Kruize, Laurence Laigle, Véronique Le Guern, Wen-Lin Luo, Esther Mossel, Wan-Fai Ng, Gaëtane Nocturne, Marleen Nys, Roald Omdal, Jacques-Olivier Pers, Maggy Pincemin, Manel Ramos-Casals, Philippe Ravaud, Neelanjana Ray, Alain Saraux, Athanasios Tzioufas, Gwenny Verstappen, Arjan Vissink, Marie Wahren-Herlenius, seror, raphaele, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), The Open University [Milton Keynes] (OU), William Harvey Research Institute, Barts and the London Medical School, University Medical Center Groningen [Groningen] (UMCG), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], NECESSITY WP5- STAR development working group : Suzanne Arends, Francesca Barone, Albin Björk, Coralie Bouillot, Guillermo Carvajal Alegria, Wen-Hung Chen, Kenneth Clark, Konstantina Delli, Liseth de Wolff, Jennifer Evans, Stéphanie Galtier, Saviana Gandolfo, Mickael Guedj, Dewi Guellec, Safae Hamkour, Dominik Hartl, Malin V Jonsson, Roland Jonsson, Frans G M Kroese, Aike Albert Kruize, Laurence Laigle, Véronique Le Guern, Wen-Lin Luo, Esther Mossel, Wan-Fai Ng, Gaëtane Nocturne, Marleen Nys, Roald Omdal, Jacques-Olivier Pers, Maggy Pincemin, Manel Ramos-Casals, Philippe Ravaud, Neelanjana Ray, Alain Saraux, Athanasios Tzioufas, Gwenny Verstappen, Arjan Vissink, Marie Wahren-Herlenius., and European Project: 806975,NECESSITY
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Consensus, [SDV]Life Sciences [q-bio], Immunology, health care, General Biochemistry, Genetics and Molecular Biology, [SDV] Life Sciences [q-bio], Rheumatology, patient reported outcome measures, Sjogren's syndrome, Outcome Assessment, Health Care, Immunology and Allergy, Humans, Rituximab, outcome assessment, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveTo develop a composite responder index in primary Sjögren’s syndrome (pSS): the Sjögren’s Tool for Assessing Response (STAR).MethodsTo develop STAR, the NECESSITY (New clinical endpoints in primary Sjögren’s syndrome: an interventional trial based on stratifying patients) consortium used data-driven methods based on nine randomised controlled trials (RCTs) and consensus techniques involving 78 experts and 20 patients. Based on reanalysis of rituximab trials and the literature, the Delphi panel identified a core set of domains with their respective outcome measures. STAR options combining these domains were proposed to the panel for selection and improvement. For each STAR option, sensitivity to change was estimated by the C-index in nine RCTs. Delphi rounds were run for selecting STAR. For the options remaining before the final vote, a meta-analysis of the RCTs was performed.ResultsThe Delphi panel identified five core domains (systemic activity, patient symptoms, lachrymal gland function, salivary gland function and biological parameters), and 227 STAR options combining these domains were selected to be tested for sensitivity to change. After two Delphi rounds, a meta-analysis of the 20 remaining options was performed. The candidate STAR was then selected by a final vote based on metrological properties and clinical relevance.ConclusionThe candidate STAR is a composite responder index that includes all main disease features in a single tool and is designed for use as a primary endpoint in pSS RCTs. The rigorous and consensual development process ensures its face and content validity. The candidate STAR showed good sensitivity to change and will be prospectively validated by the NECESSITY consortium in a dedicated RCT.
Published: 2022

13. Circulating autoreactive proteinase 3(+) B cells and tolerance checkpoints in ANCA-associated vasculitis

Author: Carol A. Langford, Paul A. Monach, Kristina M. Harris, Alvise Berti, Paul Brunetta, Robert Spiera, Jacques-Olivier Pers, Divi Cornec, E. William St. Clair, Peter Heeringa, Ulrich Specks, Philip Seo, Tobias Peikert, Sophie Hillion, Amber M. Hummel, Peter A. Merkel, Young Min Son, Nedra Chriti, Wayel H. Abdulahad, Fernando C. Fervenza, Jie Sun, Cees G. M. Kallenberg, John H. Stone, Eva M. Carmona, Guido Grandi, Translational Immunology Groningen (TRIGR), and Groningen Kidney Center (GKC)
Subjects: Male, Vasculitis, Autoimmune diseases, Immunology, BIOMARKERS, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Autoimmunity, medicine.disease_cause, Peripheral blood mononuclear cell, Flow cytometry, ACTIVATION, WEGENERS-GRANULOMATOSIS, Double-Blind Method, Memory B Cells, Proteinase 3, Medicine, Humans, cardiovascular diseases, RITUXIMAB, SPECIFICITY, biology, medicine.diagnostic_test, business.industry, RECOGNITION, MYELOPEROXIDASE, General Medicine, medicine.disease, Flow Cytometry, PR3, In vitro, Peripheral, Myeloperoxidase, ANTIBODIES, biology.protein, Female, AUTOANTIBODIES, Clinical Medicine, business, Peptide Hydrolases
Abstract: BACKGROUND Little is known about the autoreactive B cells in antineutrophil cytoplasmic antibody–associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3–reactive (PR3+) B cells. METHODS Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3+ B cells (total and subsets). RESULTS The frequency of PR3+ B cells among circulating B cells was higher in participants with PR3-AAV (4.77% median [IQR, 3.98%–6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%–5.22%]) and participants with AAV compared with HCs (1.67% median [IQR, 1.27%–2.16%], P < 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3+ B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3+ memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3+ B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3+ B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, P < 0.05) and complete remission (P < 0.001). CONCLUSION This study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells. Trial registration ClinicalTrials.gov NCT00104299. Funding The Vasculitis Foundation, the National Institute of Allergy and Infectious Diseases of the NIH, and the Mayo Foundation for Education and Research.
Published: 2021

14. The Influence of Underlying Disease on Rituximab Pharmacokinetics May be Explained by Target-Mediated Drug Disposition

Author: Emmanuel Gyan, Divi Cornec, Olivier Casasnovas, Gilles Paintaud, Denis Mulleman, Thierry Lamy, Céline Desvignes, Stéphane Leprêtre, David Ternant, Amina Bensalem, Ulrich Specks, Guillaume Cartron, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Mayo Clinic [Rochester], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Laboratory of Pathogen Host Interactions [Montpellier] (LPHI), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Follicular lymphoma, 030226 pharmacology & pharmacy, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Elimination rate constant, Antigen, immune system diseases, hemic and lymphatic diseases, medicine, Humans, Pharmacology (medical), Lymphoma, Follicular, Pharmacology, CD20, biology, business.industry, Antigens, CD20, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Lymphoma, 030220 oncology & carcinogenesis, Rheumatoid arthritis, biology.protein, Cancer research, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, medicine.drug
Abstract: International audience; BACKGROUND AND OBJECTIVES: Rituximab is an anti-CD20 monoclonal antibody approved in several diseases, including chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), rheumatoid arthritis (RA), and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The influence of underlying disease on rituximab pharmacokinetics has never been investigated for several cancer and non-cancer diseases simultaneously. This study aimed at assessing this influence using an integrated semi-mechanistic model accounting for target-mediated elimination of rituximab. METHODS: Rituximab concentration-time data from five studies previously published in patients with CLL, DLBCL, FL, RA, and AAV were described using a two-compartment model with irreversible binding of rituximab to its target antigen. Both underlying disease and target antigen measurements were assessed as covariates. RESULTS: Central volume of distribution was [95% confidence interval] 1.7-fold [1.6-1.9] higher in DLBCL than in RA, FL, and CLL, and it was 1.8-fold [1.6-2.1] higher in RA, FL, and CLL than in AAV. First-order elimination rate constants were 1.8-fold [1.7-2.0] and 1.3-fold [1.2-1.5] higher in RA, DLBCL, and FL than in CLL and AAV, respectively. Baseline latent antigen level (L(0)) was 54-fold [30-94], 20-fold [11-36], and 29-fold [14-64] higher in CLL, DLBCL, and FL, respectively, than in RA and AAV. In lymphoma, L(0) increased with baseline total metabolic tumor volume (p = 6.10(-7)). In CLL, the second-order target-mediated elimination rate constant (k(deg)) increased with baseline CD20 count on circulating B cells (CD20(cir), p = 0.0081). CONCLUSIONS: Our results show for the first time that rituximab pharmacokinetics is strongly influenced by underlying disease and disease activity. Notably, neoplasms are associated with higher antigen amounts that result in decreased exposure to rituximab compared to inflammatory diseases. Our model might be used to estimate unbound target amounts in upcoming studies.
Published: 2021

15. Identifying clinical, biological, and quality of life variables associated with depression, anxiety, and fatigue in pSS and sicca syndrome patients: a prospective single-centre cohort study

Author: Louise Miglianico, Divi Cornec, Valérie Devauchelle-Pensec, Sofian Berrouiguet, Michel Walter, Patrice Nabbé, Eléonore Bettacchioli, and Florian Stéphan
Subjects: Cohort Studies, Sjogren's Syndrome, Rheumatology, Depression, Quality of Life, Humans, Prospective Studies, Anxiety, Fatigue
Published: 2022

16. Lack of association between the TNFAIP3 rs2230926 variant and rheumatoid arthritis-associated lymphoma

Author: Joanna Kedra, Raphaele Seror, Philippe Dieudé, Arnaud Constantin, Eric Toussirot, Elias Kfoury, Charles Masson, Divi Cornec, Jean-Jacques Dubost, Laurent Marguerie, Sebastien Ottaviani, Franck Grados, Rakiba Belkhir, Olivier Fain, Bruno Fautrel, Peggy Philippe, Muriel Piperno, Bernard Combe, Olivier Lambotte, Christophe Richez, Jérémie Sellam, Thomas Sené, Guillaume Denis, Thierry Lequerre, Thierry Lazure, Xavier Mariette, and Gaetane Nocturne
Subjects: Arthritis, Rheumatoid, Lymphoma, Rheumatology, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Tumor Necrosis Factor alpha-Induced Protein 3
Published: 2022

17. Histological and imaging characteristics of acute colchicine myotoxicity

Author: Baptiste Quéré, Amélie Bourhis, Pascale Marcorelles, Arnaud Uguen, Jean-Baptiste Noury, Zarrin Alavi, Divi Cornec, and Dewi Guellec
Subjects: Rheumatology, Fluorodeoxyglucose F18, Positron-Emission Tomography, Humans, Myotoxicity, Radiopharmaceuticals, Colchicine
Published: 2021

18. Practical Management of patients on anti-IL6R therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author: Jacques Morel, Anne Tournadre, Jérémie Sellam, Yoram Bouhnik, Divi Cornec, Valérie Devauchelle-Pensec, Philippe Dieudé, Philippe Goupille, Nicolas Kluger, Estibaliz Lazaro, Benoit Le Goff, Victor de Lédinghen, Thierry Lequerré, Gaëtane Nocturne, Raphaèle Seror, Marie-Elise Truchetet, Frank Verhoeven, Thao Pham, and Christophe Richez
Subjects: Arthritis, Rheumatoid, Inflammation, Rheumatology, Antirheumatic Agents, Humans
Published: 2021

19. Practical management of patients on anti-IL17 therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author: Anne Tournadre, Jérémie Sellam, Jacques Morel, Denis Jullien, Yoram Bouhnik, Divi Cornec, Valérie Devauchelle-Pensec, Philippe Goupille, Nicolas Kluger, Estibaliz Lazaro, Benoit Le Goff, Victor de Lédinghen, Thierry Lequerré, Gaëtane Nocturne, Raphaèle Seror, Marie-Elise Truchetet, Frank Verhoeven, Christophe Richez, Thao Pham, Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de dermatologie [HCL Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Gastro-entérologie, CHU Hôpital Beaujon, Clichy, France, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Dermatologie [Hôpital Bichat – Claude-Bernard - APHP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et maladies infectieuses, CHU de Bordeaux, F-33600, Pessac, Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité d'Hépatologie et transplantation hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Rhumatologie, Bicêtre, Le Kremlin-Bicêtre, France, Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Rhumatologie Bordeaux (SERVICE DE RHUMATOLOGIE), CHU Bordeaux [Bordeaux], and Service de Rhumatologie, Hôpital Sainte-Marguerite, Aix Marseille
Subjects: 030203 arthritis & rheumatology, Arthritis, Rheumatoid, Inflammation, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Antirheumatic Agents, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: International audience
Published: 2021

20. PRACTICAL MANAGEMENT of patients on anti-TNF therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author: Marie-Elise Truchetet, Anne Tournadre, Estibaliz Lazaro, Jacques Morel, Raphaèle Seror, Philippe Dieudé, Denis Jullien, Thao Pham, Philippe Goupille, Thierry Lequerré, Valérie Devauchelle-Pensec, Jérémie Sellam, Gaetane Nocturne, Yoram Bouhnik, Victor de Lédinghen, Divi Cornec, Christophe Richez, Nicolas Kluger, Benoit Le Goff, Frank Verhoeven, 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), Service de Rhumatologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), GH Bichat - Service de Rhumatologie, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Service de Dermatologie [Hôpital Bichat – Claude-Bernard - APHP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Médecine Interne [CHU de Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU de Bordeaux], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité d'Hépatologie et transplantation hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Service de Rhumatologie, Hôpital Sainte-Marguerite, Aix Marseille
Subjects: 030203 arthritis & rheumatology, Inflammation, medicine.medical_specialty, business.industry, MEDLINE, 3. Good health, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Antirheumatic Agents, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Tumor Necrosis Factor Inhibitors, 030212 general & internal medicine, Club, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

21. Non-Linear Rituximab Pharmacokinetics and Complex Relationship between Rituximab Concentrations and Anti-Neutrophil Cytoplasmic Antibodies (ANCA) in ANCA-Associated Vasculitis: The RAVE Trial Revisited

Author: David Ternant, Valérie Gouilleux-Gruart, Gilles Paintaud, Ulrich Specks, Nicolas Azzopardi, Amina Bensalem, Denis Mulleman, Divi Cornec, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Pharmacologie Médicale [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire d'Immunologie Tours, 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), Mayo Clinic and Mayo College of Medicine, Rochester, Laboratoire de Pharmacologie-Toxicologie [CHRU Tours], Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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: Male, urologic and male genital diseases, 030226 pharmacology & pharmacy, Antineoplastic Agents, Immunological, 0302 clinical medicine, Elimination rate constant, immune system diseases, Medicine, Pharmacology (medical), Infusions, Intravenous, skin and connective tissue diseases, Aged, 80 and over, education.field_of_study, biology, Remission Induction, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, Antibody, Vasculitis, medicine.drug, Adult, Myeloblastin, Population, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Models, Biological, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, Pharmacotherapy, Double-Blind Method, Pharmacokinetics, Humans, cardiovascular diseases, education, Aged, Peroxidase, Pharmacology, business.industry, medicine.disease, respiratory tract diseases, Nonlinear Dynamics, Immunology, biology.protein, business, Neutrophil cytoplasmic, Biomarkers
Abstract: Rituximab is approved in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and leads to a decrease of ANCA levels. The objectives of this study were to investigate the non-linear pharmacokinetics of rituximab and the relationship between its concentrations and ANCA levels in AAV patients. Ninety-two AAV patients from the RAVE (Rituximab in ANCA-Associated Vasculitis) trial were assessed. Both ANCA anti-myeloperoxidase (MPO-ANCA) and anti-proteinase 3 (PR3-ANCA) levels were used as biomarkers. The pharmacokinetics of rituximab were described using a semi-mechanistic two-compartment model that included a latent target antigen turnover and allowed the estimation of specific target-mediated elimination in addition to its non-specific elimination of rituximab. The effect of rituximab on the ANCA level was described using a semi-mechanistic compartment model with a negative feedback (Friberg) model with no transit compartment. A population modeling approach was used. Our pharmacokinetic and pharmacokinetic–pharmacodynamic (PK-PD) models satisfactorily described both concentration–time and concentration–effect relationship data. The mean (inter-individual standard deviation) estimated non-specific clearance was 0.15 L/day (0.30%) and the target-mediated elimination rate constant was 2.4 × 10−5 nmol/day. The elimination half-lives for MPO-ANCA and PR3-ANCA were 24 and 18 days, respectively. A non-linear target-mediated elimination of rituximab was detected in AAV patients. Our PK-PD model allowed quantification of the association between rituximab concentrations and ANCA levels. This decrease was deep but delayed, and more sustained in patients with MPO-ANCA than in those with PR3-ANCA. Our results suggest that repeating courses of rituximab might improve the clinical response to rituximab.
Published: 2019

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

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

23. Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis

Author: Antonello, Veccia, Marie, Kostine, Alice, Tison, Mariachiara, Dipasquale, Stefania, Kinspergher, Larry, Prokop, Guido, Grandi, Sandro, Inchiostro, Orazio, Caffo, Giuseppe, Paolazzi, Roberto, Bortolotti, Divi, Cornec, and Alvise, Berti
Subjects: Antineoplastic Agents, Immunological, Lung Neoplasms, Rheumatology, Humans, Arthralgia
Abstract: We aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature.We performed a systematic review and meta-analysis of phase III randomized clinical trials (RCTs) assessing PD-(L)1-ICIs in lung cancer patients, from inception until January 12th, 2021. We extracted data of each trial to estimate odds ratio (OR) for rheumatic ir or non-irAE as classified in RCTs safety data. Sensitivity analyses (by ICI, treatment group and histology) were performed.Eighteen RCTs met the inclusion criteria (n=12172 subjects). The OR [95%IC] for rheumatic irAE in ICIs versus controls (either placebo or chemotherapy) was 2.20 [0.85,5.72]. Among rheumatic non-irAEs, both overall and severe (grade≥3) back pain were significantly more frequent in ICIs versus controls, 2.01 [1.09;3.73] and 2.90 [1.18;7.08], respectively. The overall frequency of arthralgia was similar between ICIs and controls; by sensitivity analysis RCTs assessing ICIs in combination with chemotherapy showed a significant association with arthralgia (1.55 [1.15;2.10]). Similarly, the frequency of myalgia was significantly lower in RCTs assessing ICIs alone versus chemotherapy (OR 0.32 [0.24;0.42]). Muscular pain was not significantly increased with ICI.Rheumatic irAEs are not increased in RCTs assessing PD-(L)1 inhibitors, not reflecting the real-life incidence, therefore likely underreported or misclassified. Back pain is significantly associated with them regardless its severity, while arthralgia only when ICIs are added on conventional chemotherapy.
Published: 2022

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

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

25. Venous thrombosis and predictors of relapse in eosinophil-related diseases

Author: Matthieu Groh, Francisco Osorio-Perez, Benjamin Terrier, Aurélie Plessier, Divi Cornec, Julien Rohmer, Marc Vasse, Nathalie Freymond, Mohamed Hamidou, Ruben Benainous, Stanislas Faguer, Alexandre Vallée, Marie-Laure Chabi-Charvillat, Elina Zuelgaray, Felix Ackermann, Jean-Emmanuel Kahn, Guy Meyer, A.C. Desbois, Martin Killian, Valériane Réau, Nicolas Simon, G. Bohelay, Noémie Abisror, Sylvain Le Jeune, Guillaume Lefèvre, Colas Tcherakian, Pierre-Emmanuel Rautou, Kewin Panel, Antoine Gaillet, Anne Marchetti, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Hôpital Foch [Suresnes], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Avicenne [AP-HP], Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Toulouse [Toulouse], CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier de Dax, Centre Hospitalier Universitaire [Grenoble] (CHU), Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Hopital Saint-Louis [AP-HP] (AP-HP), CHU Lille, Hôpital Ambroise Paré [AP-HP], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and HAL-SU, Gestionnaire
Subjects: Male, 0301 basic medicine, Churg-Strauss Syndrome, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Recurrence, Hypereosinophilic Syndrome, Eosinophilic, Eosinophilia, Venous Thrombosis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Leukemia, Multidisciplinary, Portal Vein, Hypereosinophilic syndrome, Middle Aged, 3. Good health, Pulmonary embolism, Venous thrombosis, Treatment Outcome, medicine.anatomical_structure, Medicine, Female, medicine.symptom, Eosinophilic vasculitis, Granulomatosis with polyangiitis, Adult, medicine.medical_specialty, Science, Article, 03 medical and health sciences, Medical research, Internal medicine, medicine, Humans, Aged, Retrospective Studies, mRNA Cleavage and Polyadenylation Factors, business.industry, Eosinophil, medicine.disease, Eosinophils, 030104 developmental biology, Risk factors, Pulmonary Embolism, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.
Published: 2021

26. Impact of the COVID-19 pandemic on therapeutic management of rheumatoid arthritis in Brittany (France)

Author: Divi Cornec, Margot Le Guillou, Maxime Quiviger, Dewi Guellec, Valérie Devauchelle-Pensec, Baptiste Queré, Alain Saraux, Guillermo Carvajal Alegria, Camille Houssais, Sandrine Jousse-Joulin, and Thierry Marhadour
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, medicine.disease, Virology, Article, Arthritis, Rheumatoid, Rheumatology, Rheumatoid arthritis, Pandemic, medicine, Humans, France, business, Pandemics
Published: 2021

27. Temporal Artery Ultrasound to Diagnose Giant Cell Arteritis: A Practical Guide

Author: Sandrine Jousse-Joulin, Steve Raoul Noumegni, Clément Hoffmann, Divi Cornec, Luc Bressollette, Simon Gestin, Unité d'Echo-Doppler et de Médecine Vasculaire (BREST - ED MV), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato)
Subjects: medicine.medical_specialty, Acoustics and Ultrasonics, Biophysics, Diagnostic tools, Diagnostic modalities, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, immune system diseases, Ultrasound, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, 030212 general & internal medicine, Ultrasonography, Doppler, Color, skin and connective tissue diseases, Giant cell arteritis, 030203 arthritis & rheumatology, Radiological and Ultrasound Technology, business.industry, Temporal arteries, Doppler, Reproducibility of Results, medicine.disease, symbols, cardiovascular system, [SDV.IMM]Life Sciences [q-bio]/Immunology, Temporal artery, Doppler ultrasound, Radiology, business, Doppler effect
Abstract: International audience; The diagnostic modalities for giant cell arteritis (GCA) have evolved significantly in recent years. Among the different diagnostic tools developed, Doppler ultrasound of the temporal arteries, with a sensitivity and specificity reaching 69% and 82%, respectively, is now recognized as superior and, therefore, is a first-line diagnostic tool in GCA. Moreover, with the increasing development of new ultrasound technologies, the accuracy of Doppler ultrasound in GCA seems to be constantly improving. In this article, we describe in detail the scanning technique to perform while realizing Doppler ultrasound of temporal arteries to assess GCA, as well as the diagnostic performance of this tool according to current literature.
Published: 2021

28. Epidemiology of cutaneous involvement in Sjögren syndrome: Data from three French pSS populations (TEARS, ASSESS, diapSS)

Author: Raphaèle Seror, Laurent Misery, Philippe Dieudé, Eric Hachulla, Xavier Mariette, Gilles Hayem, Jacques-Eric Gottenberg, Camille Villon, Aleth Perdriger, Laure Orgeolet, Jean-Jacques Dubost, Divi Cornec, Jacques Morel, Pierre-Yves Hatron, Jean-Marie Berthelot, Vincent Goëb, Anne-Laure Fauchais, Valérie Devauchelle-Pensec, Véronique Le Guern, Sandrine Jousse-Joulin, Olivier Vittecoq, Claire Larroche, Alain Saraux, Anne-Marie Roguedas, CHRU de Brest - Département de dermatologie, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], 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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Rhumatologie (Rhumato - BICHAT), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Gabriel-Montpied], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Service de Rhumatologie - AMIENS (AMIENS - Rhumato), CHU Amiens-Picardie, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Oust de France (CeRAINO), F-59000, Lille, Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Département de Rhumatologie (Rhumato - Ambroise Paré - PARIS), Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Unité thérapeutique d'immunologie clinique et des maladies ostéoarticulaires [Hôpital Lapeyronie, Montpellier], Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), and Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche)
Subjects: medicine.medical_specialty, Visual analogue scale, Placebo, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Dry skin, medicine, Prevalence, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Pain Measurement, 030203 arthritis & rheumatology, integumentary system, business.industry, Hypergammaglobulinemia, medicine.disease, Dermatology, eye diseases, 3. Good health, stomatognathic diseases, Sjogren's Syndrome, Cohort, Tears, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, medicine.symptom, business, medicine.drug
Abstract: To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS).We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100).Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P0.001), muscular (P0.01), haematological (P0.05), biological (P0.05), history of arthritis (P0.01), splenomegaly (P0.05) and higher gamma globulin levels (P0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS50; 48.2%) and found that patients with dry skin had higher VAS pain (P0.01) and drought (P0.01) scores.ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.
Published: 2020

29. Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series

Author: Frank Verhoeven, Renaud Felten, Daniel Wendling, Martin Soubrier, Alain Saraux, Eric Toussirot, Jean Sibilia, Charles Dervout, V. Grobost, Bruno Gombert, Divi Cornec, Hervé Lobbes, Marc Ruivard, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), FHU 'Integrated center for research in inflammatory diseases - InCREASe', Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Equipe Plate-forme GENOMAX (Inserm U1109), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Besançon, Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CCSD, Accord Elsevier, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Lymphocyte B et Auto-immunité (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: medicine.medical_specialty, Cyclophosphamide, [SDV.IMM] Life Sciences [q-bio]/Immunology, Large granular lymphocytic leukemia, Population, Gastroenterology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Cyclosporin a, medicine, Humans, Rheumatoid factor, 030212 general & internal medicine, education, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Middle Aged, medicine.disease, 3. Good health, Leukemia, Large Granular Lymphocytic, Methotrexate, Anesthesiology and Pain Medicine, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, business, medicine.drug
Abstract: Objectives To assess the efficacy and tolerance profile of rituximab in rheumatoid arthritis (RA)-associated large granular lymphocyte leukemia (LGLL). Methods Multicenter retrospective case series. Inclusion criteria were RA defined by the ACR/EULAR 2010 criteria and LGLL defined by absolute LGL count ≥ 0.3 × 109/L with evidence of an expanded clonal LGL population (flow cytometry, TCR-γ polymerase chain reaction, or Stat3 mutation). Results Fourteen patients (10 women, mean age 55.2 ± 14.2 years) included; 13 were seropositive for anti-cyclic citrullinated peptides (n = 11) or rheumatoid factor (n = 10). LGLL diagnosis was made 9.5 [IQR: 3.25;15.5] years after RA diagnosis. Thirteen patients had T-LGLL. Rituximab was the first-line therapy for LGLL for 4 patients. Previous treatment lines included methotrexate (n = 7), cyclophosphamide (n = 2), cyclosporin A (n = 1), or granulocyte colony-stimulating factor (n = 4). Rituximab was used in monotherapy (n = 8) or associated to methotrexate (n = 3), granulocyte colony-stimulating factor (n = 2), or alkylating agents (n = 1). The number of rituximab cycles ranged from 1 to 11 (median 6), with high heterogeneity in dosing regimens. Median duration response after rituximab initiation was 35 [IQR: 23.5;41] months. The overall response rate was 100%: 8 patients experienced complete response (normalization of blood count and LGL ≤ 0.3 × 109/L) and 6 experienced partial responses (improvement in blood counts without complete normalization). The tolerance profile was good, with no infectious complications. Conclusion rituximab appears as a valuable therapeutic option for RA-associated LGLL.
Published: 2020

30. Should the Biopsychosocial Model Be Considered in Systemic Autoimmune Diseases? Comment on the Article by Posada et al

Author: Divi Cornec, Laurent Chiche, and Noémie Jourde-Chiche
Subjects: Biopsychosocial model, Psychotherapist, business.industry, Immunology, MEDLINE, Models, Biopsychosocial, Autoimmune Diseases, Sjogren's Syndrome, Rheumatology, Immunology and Allergy, Medicine, Humans, business, Fatigue
Published: 2020

31. Refining myositis associated with primary Sjögren’s syndrome: data from the prospective cohort ASSESS

Author: Emmanuelle Dernis, Raphaèle Seror, Eric Hachulla, Divi Cornec, Claire Larroche, Philippe Dieudé, Olivier Vittecoq, Alain Meyer, Jean-Jacques Dubost, Aleth Perdriger, Dan Levy, Véronique Le Guern, Benoit Nespola, Dewi Guellec, Jacques-Eric Gottenberg, Béatrice Lannes, Jean Sibilia, Renaud Felten, Anne-Laure Fauchais, Margherita Giannini, Xavier Mariette, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Pôle de Biologie - Laboratoire d’Immunologie [Nouvel Hôpital Civil, Strasbourg] (Plateau Technique de Biologie), Nouvel Hôpital Civil - NHC [Strasbourg], Service de pathologie [CHU Strasbourg], CHU Strasbourg, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de Médecine Interne et Immunologie Clinique, CHU Lille, F-59037, Lille Cedex, Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], GH Bichat - Service de Rhumatologie, Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: Male, Time Factors, dermatomyositis, Systemic scleroderma, Polymyositis, polymyositis, 0302 clinical medicine, inflammatory myopathies, Pharmacology (medical), Prospective Studies, Prospective cohort study, Myositis, health care economics and organizations, Aged, 80 and over, inclusion body myositis, Middle Aged, Prognosis, 3. Good health, Peeling skin syndrome, Sjogren's Syndrome, Cohort, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, musculoskeletal diseases, Adult, medicine.medical_specialty, Adolescent, education, 03 medical and health sciences, Young Adult, Rheumatology, stomatognathic system, Internal medicine, medicine, Humans, Patient Reported Outcome Measures, Glucocorticoids, Aged, Autoantibodies, 030203 arthritis & rheumatology, business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Dermatomyositis, medicine.disease, eye diseases, stomatognathic diseases, Methotrexate, Sjögren’s syndrome, Inclusion body myositis, business, myositis, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Objectives To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). Methods The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months’ follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. Results Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested ‘pure’ pSS myositis. Steroids plus MTX was then efficient in achieving remission. Conclusions Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.
Published: 2020

32. Tocilizumab controls bone turnover in early polymyalgia rheumatica

Author: Florent Garrigues, Divi Cornec, Alain Saraux, Valérie Devauchelle-Pensec, D. Loeuille, Yves Renaudineau, Eléonore Bettacchioli, and Guillermo Carvajal Alegria
Subjects: musculoskeletal diseases, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Gastroenterology, Collagen Type I, Bone remodeling, Polymyalgia rheumatica, chemistry.chemical_compound, Tocilizumab, Rheumatology, Bone Density, Internal medicine, medicine, Humans, In patient, Prospective Studies, skin and connective tissue diseases, Interleukin 6, Bone mineral, Collagen type, biology, business.industry, Interleukin, medicine.disease, Peptide Fragments, chemistry, Polymyalgia Rheumatica, biology.protein, Bone Remodeling, business, Biomarkers
Abstract: This study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR).Twenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients.PMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P=0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r=0.255 at W0 versus r=0.641 in healthy controls) and its correction after treatment (r=0.760 at W12 and r=0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy.Control of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.
Published: 2020

33. Aortic involvement in giant cell arteritis

Author: Guillermo Carvajal Alegria, Divi Cornec, Maria Sandovici, Jacoba Carolien Graver, Yannick van Sleen, Valérie Devauchelle-Pensec, Elisabeth Brouwer, Translational Immunology Groningen (TRIGR), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Aorta, Pathology, medicine.medical_specialty, business.industry, Dissection, Giant Cell Arteritis, Dissection (medical), medicine.disease, Aneurysm, Imaging, Giant cell arteritis, Rheumatology, medicine.artery, medicine, Humans, business
Published: 2020

34. Immune-checkpoint inhibitors to treat cancers in specific immunocompromised populations: a critical review

Author: Gilles Quere, Divi Cornec, Renaud Descourt, Alice Tison, Luca Lanfranco, Hélène Babey, Ronan Le Calloch, Christos Chouaid, and Jean-Baptiste Nousbaum
Subjects: Programmed cell death, Immune checkpoint inhibitors, Human immunodeficiency virus (HIV), medicine.disease_cause, Immunocompromised Host, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Neoplasms, Animals, Humans, Medicine, CTLA-4 Antigen, Pharmacology (medical), Clinical Trials as Topic, business.industry, Antibodies, Monoclonal, Cancer, medicine.disease, Transplant Recipients, Oncology, 030220 oncology & carcinogenesis, Monoclonal, Cancer research, business, 030215 immunology
Abstract: Because of their efficacy against numerous cancers, immune-checkpoint inhibitors (ICIs), anti-cytotoxic T-lymphocyte antigen-4, and anti-programmed cell death monoclonal antibodies are being used ever more often in oncology. However, some patients were excluded from clinical trials because of their comorbidities despite their potentially higher cancer frequencies, as is the case for immunocompromised patients. Areas covered: We analyzed reported preclinical and clinical information and evaluated the risk/benefit ratio for four immunocompromised populations: people living with human immunodeficiency virus (PLHs), solid-organ transplant recipients, recipients of hematopoietic stem-cell allografts, and patients with autoimmune diseases. Expert commentary: Information available in the literature is fragmentary and scarce, making it difficult to evaluate the risk/benefit ratio. It can, nonetheless, be noted that ICI use in PLHs seems possible. For solid-organ transplant recipients, the risk for the graft seems elevated. For the other two populations, it is difficult to conclude at this time.
Published: 2018

35. Pharmacokinetics of rituximab and clinical outcomes in patients with anti-neutrophil cytoplasmic antibody associated vasculitis

Author: Paul A. Monach, Robert Spiera, Paul Brunetta, Darrell R. Schroeder, Ulrich Specks, Amber M. Hummel, Matthew D Cascino, David R. Barnidge, David L. Murray, Brian Kabat, Melissa R. Snyder, Cees G. M. Kallenberg, Fernando C. Fervenza, Philip Seo, Carol A. Langford, Peter A. Merkel, E. William St. Clair, John Mills, John H. Stone, Divi Cornec, Gary S. Hoffman, and Melissa Cheu
Subjects: 0301 basic medicine, Male, ANCA-ASSOCIATED VASCULITIS, MONOCLONAL-ANTIBODY, outcomes, DISEASE-ACTIVITY, RELAPSE, Gastroenterology, law.invention, 0302 clinical medicine, rituximab, Maintenance therapy, Randomized controlled trial, law, LYMPHOMA, Pharmacology (medical), Infusions, Intravenous, Body surface area, UTILITY, B-Lymphocytes, Remission Induction, Area under the curve, Middle Aged, Clinical Science, Treatment Outcome, Rituximab, Female, Vasculitis, pharmacokinetics, medicine.drug, Adult, medicine.medical_specialty, MAINTENANCE THERAPY, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, 03 medical and health sciences, Rheumatology, Pharmacokinetics, Double-Blind Method, Internal medicine, medicine, Humans, Immunologic Factors, Lymphocyte Count, EXPOSURE, Anti-neutrophil cytoplasmic antibody, Aged, 030203 arthritis & rheumatology, Dose-Response Relationship, Drug, business.industry, RHEUMATOID-ARTHRITIS PATIENTS, MASS-SPECTROMETRY, medicine.disease, 030104 developmental biology, business
Abstract: Objectives. To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes.Methods. This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m(2)). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by computing the trapezoidal area under the curve. We explored potential determinants of the PK-RTX, and analysed its association with clinical outcomes: achievement of remission at 6 months, duration of B-cell depletion and time to relapse in patients who achieved complete remission.Results. RTX serum levels were significantly lower in males and in newly diagnosed patients, and negatively correlated with body surface area, baseline B-cell count and degree of disease activity. In multivariate analyses, the main determinants of PK-RTX were sex and new diagnosis. Patients reaching complete remission at month 6 had similar RTX levels compared with patients who did not reach complete remission. Patients with higher RTX levels generally experienced longer B-cell depletion than patients with lower levels, but RTX levels at the different time points and area under the curve were not associated with time to relapse.Conclusion. Despite the body-surface-area-based dosing protocol, PK-RTX is highly variable among patients with AAV, its main determinants being sex and newly diagnosed disease. We did not observe any relevant association between PK-RTX and clinical outcomes. The monitoring of serum RTX levels does not seem clinically useful in AAV.
Published: 2018

36. The Epidemiology of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Olmsted County, Minnesota

Author: Ulrich Specks, Divi Cornec, Eric L. Matteson, Cynthia S. Crowson, and Alvise Berti
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Minnesota, Myeloblastin, Immunology, Population, Microscopic Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Churg-Strauss Syndrome, Article, Antibodies, Antineutrophil Cytoplasmic, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Prevalence, medicine, Humans, Immunology and Allergy, cardiovascular diseases, 030212 general & internal medicine, education, Survival rate, Aged, Peroxidase, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Incidence, Incidence (epidemiology), Mortality rate, Granulomatosis with Polyangiitis, Middle Aged, medicine.disease, 3. Good health, Survival Rate, Cohort, Female, Microscopic polyangiitis, Granulomatosis with polyangiitis, business, Cohort study
Abstract: Objective To estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) and its subsets, granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), in a US-based adult population. Methods All medical records of patients with a diagnosis of, or suspicion of having, AAV in Olmsted County, Minnesota from January 1, 1996 to December 31, 2015 were reviewed. AAV incidence rates were age- and sex-adjusted to the 2010 US white population. Age- and sex-adjusted prevalence of AAV was calculated on January 1, 2015. Survival rates observed in the study cohort were compared with expected rates in the Minnesota population. Results Of the 58 incident cases of AAV in Olmsted County during the study period, 23 (40%) were cases of GPA, 28 (48%) were cases of MPA, and 7 (12%) were cases of EGPA. Overall, 28 (48%) of the patients with AAV were women and 57 (98%) were white. The mean ± SD age at diagnosis was 61.1 ± 16.5 years. Thirty-four patients (61%) had myeloperoxidase (MPO)–ANCAs, and 17 (30%) were positive for proteinase 3 (PR3)–ANCAs; 5 (9%) were ANCA-negative. The annual incidence of AAV was 3.3 per 100,000 population (95% confidence interval [95% CI] 2.4–4.1). The incidence rates of GPA, MPA, and EGPA were 1.3 (95% CI 0.8–1.8), 1.6 (95% CI 1.0–2.2), and 0.4 (95% CI 0.1–0.6), respectively. The overall prevalence of AAV was 42.1 per 100,000 (95% CI 29.6–54.6). The mortality rate among AAV patients overall, and among patients with EGPA, those with MPA, and those with MPO-ANCAs, was increased in comparison to the Minnesota general population (each P < 0.05), whereas mortality rates among patients with GPA, those with PR3-ANCAs, and ANCA-negative patients did not differ from that in the general population. Conclusion The annual incidence of AAV in Olmsted County, Minnesota over the 20 years of the study was 3.3 per 100,000, with a prevalence of 42.1 per 100,000, which is substantially higher than the rates reported in other areas worldwide. The incidence of GPA was similar to that of MPA. Patients with MPA and those with EGPA, but not patients with GPA, experienced higher rates of mortality than that in the Minnesota general population. MPO-ANCAs were a marker of poor survival in this population of patients with AAV.
Published: 2017

37. Dr. Berti et al reply

Author: Alvise Berti, Eric L. Matteson, Divi Cornec, Cynthia S. Crowson, University of Trento [Trento], Santa Chiara Hospital, Rheumatology Clinic, Santa Chiara Hospital, Trento, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Mayo Clinic [Rochester]
Subjects: musculoskeletal diseases, Inverse Association, medicine.medical_specialty, business.industry, Smoking, education, Immunology, Sjögren syndrome, medicine.disease, Obesity, eye diseases, 3. Good health, stomatognathic diseases, Sjogren's Syndrome, stomatognathic system, Rheumatology, Internal medicine, medicine, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunology and Allergy, Smoking status, business
Abstract: International audience; We read with interest the comment of Dr. Kawada1 on our article that showed an inverse association between current smoking status and primary (p-) Sjögren syndrome (SS), and no association between obesity and pSS.2.
Published: 2021

38. Lymphoma complicating rheumatoid arthritis: results from a French case–control study

Author: Peggy Philippe, Elias Kfoury, Xavier Mariette, Rakiba Belkhir, Thomas Sené, Divi Cornec, Bruno Fautrel, Gaetane Nocturne, Olivier Fain, Philippe Dieudé, Bernard Combe, Franck Grados, Philippe Goupille, Christelle Sordet, Jérémie Sellam, Arnaud Constantin, Muriel Piperno, Joanna Kedra, Guillaume Denis, Olivier Lambotte, Sébastien Ottaviani, Charles Masson, Jean Jacques Dubost, Christophe Richez, Laurent Marguerie, Raphaèle Seror, Thierry Lequerré, Thierry Lazure, Eric Toussirot, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de Brive-la-Gaillarde (CH Brive), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Clermont-Ferrand, Institut Calot [Fondation Hopale], CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], CHU Strasbourg, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU de Bordeaux Pellegrin [Bordeaux], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier de Rochefort (CH Rochefort), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), 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), Centre Hospitalier Brive-la-Gaillarde, Service de rhumatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], Centre Hospitalier de Rochefort, HAL-SU, Gestionnaire, Institut Calot, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre de Recherche Saint-Antoine (CR Saint-Antoine), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP]
Subjects: Male, Epstein-Barr Virus Infections, Herpesvirus 4, Human, medicine.medical_specialty, Lymphoma, rheumatoid, Immunology, Arthritis, Rheumatoid Arthritis, Gastroenterology, Arthritis, Rheumatoid, Rheumatology, immune system diseases, hemic and lymphatic diseases, Internal medicine, Epidemiology, B-lymphocytes, Humans, Immunology and Allergy, Medicine, Rheumatoid factor, Univariate analysis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Case-control study, medicine.disease, 3. Good health, arthritis, Case-Control Studies, Rheumatoid arthritis, Cohort, epidemiology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives To study the characteristics of B-cell non-Hodgkin’s lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. Methods A multicentre case–control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. Results 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. Conclusion Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.
Published: 2021

39. Lymphocytes as Biomarkers of Therapeutic Response in Rheumatic Autoimmune Diseases, Is It a Realistic Goal?

Author: Gaetane Nocturne, Kristina Schreiber, Claire Daien, Divi Cornec, Hôpital Lapeyronie [Montpellier] (CHU), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Lapeyronie [Montpellier] ( CHU ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Multivariate analysis, Lymphocyte, Cell Separation, Biomarkers, Pharmacological, Autoimmune Diseases, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Rheumatic Diseases, Internal medicine, medicine, Animals, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Mass cytometry, Lymphocyte Count, Lymphocytes, 10. No inequality, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, Reproducibility of Results, General Medicine, Flow Cytometry, Prognosis, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Rheumatoid arthritis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biomarker (medicine), Rituximab, Personalized medicine, business, medicine.drug
Abstract: Many therapies are available for patients with rheumatoid arthritis (RA) while biological therapies have limited effects in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). In both cases, biomarkers predicting drug response would be very useful to guide clinicians in their choice. We performed a systematic review to evaluate the value of lymphocyte phenotyping as a marker of therapeutic response. Of the 1063 articles retrieved, 39 fulfilled inclusion criteria and were included in the present review (25 for RA, 10 for SLE, and 4 for pSS). Lymphocyte phenotyping was described as a biomarker of therapeutic response in many studies, but most results could not be confirmed by independent teams using multivariate analysis. The most consistent result might be the association between rituximab response and the levels of memory B cells before therapy, although some studies were controversial. Thus, lymphocyte phenotyping cannot yet be proposed as a biomarker of response in rheumatic autoimmune diseases. The lack of reproducibility between studies may be explained by technical issues influencing lymphocyte phenotyping so standardization procedures should be developed for future studies. The patients' characteristics vary between studies, and large population studies, including a wide range of patients' characteristics and biomarkers, are required to provide predictive models for clinical outcomes. The use of new flow cytometry techniques such as single-cell mass cytometry technology might also help finder reliable biomarkers in the future.
Published: 2017

40. Reply

Author: Divi Cornec, Alice Tison, and Marie Kostine
Subjects: Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Autoimmune Diseases, Cohort Studies, Rheumatology, Cancer immunotherapy, Internal medicine, Neoplasms, medicine, Immunology and Allergy, Humans, In patient, business
Published: 2019

41. Eosinophilic Granulomatosis With Polyangiitis: Clinical Predictors of Long-term Asthma Severity

Author: Alvise, Berti, Divi, Cornec, Marta, Casal Moura, Robert J, Smyth, Lorenzo, Dagna, Ulrich, Specks, and Karina A, Keogh
Subjects: Male, Risk Factors, Eosinophilia, Granulomatosis with Polyangiitis, Humans, Female, Middle Aged, Severity of Illness Index, Asthma, Retrospective Studies
Abstract: The long-term clinical course of asthma in patients with eosinophilic granulomatosis with polyangiitis (EGPA) remains unclear. We aimed to characterize long-term asthma in EGPA and to identify baseline predictors of long-term asthma severity.This retrospective cohort study included patients who fulfilled standardized criteria for EGPA who were followed up in a single referral center between 1990 and 2017. Baseline and 3 (± 1) years of follow-up clinical, laboratory, and pulmonary function data were analyzed.Eighty-nine patients with EGPA and a documented asthma assessment at baseline and at 3 years from diagnosis were included. Severe/uncontrolled asthma was observed in 42.7% of patients at diagnosis and was associated with previous history of respiratory allergy (P .01), elevated serum total IgE levels (P .05), and increased use of high-dose inhaled corticosteroids (ICSs; P .05) and oral corticosteroids (OCSs; P .001) for respiratory symptoms the year before the EGPA diagnosis. During follow-up, an improvement or worsening in asthma severity was noted in 12.3% and 10.1% of patients, respectively. Severe/uncontrolled asthma was present in 40.5% of patients at 3 years and was associated with increased airway resistance on pulmonary function tests (PFTs; P .05). Long-term PFTs did not improve during long-term follow-up regardless of ICS or OCS therapy. Multivariate binary logistic regression results indicated that severe rhinosinusitis (P = .038), pulmonary infiltrates (P = .011), overweight (BMI ≥ 25 kg/mIn patients with asthma with EGPA, long-term severe/uncontrolled asthma is associated with baseline pulmonary and ear, nose, and throat manifestations but not with clear-cut vasculitic features.
Published: 2019

42. Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Preexisting Autoimmune Disease: A Nationwide Multicenter Cohort Study

Author: François-Xavier Danlos, Club Rhumatismes et Inflammations, Catherine Dubos, Thierry Lesimple, Gilles Gonzales, Julie De Quatrebarbes, Laurent Misery, Florence Brunet-Possenti, Marie Kostine, Emmanuel Nowak, Mickaël Lambert, Elisa Funck-Brentano, Laurent Chiche, Stéphanie Martinez, Sandrine Mansard, Hélène Doubre, Marie Marcq, Camille Scalbert, Yohann Loriot, Olivier Lambotte, Sarah Maanaoui, Gwenaelle Le Garff, Marie Beylot-Barry, Christos Chouaid, Jean-Bernard Auliac, Anne Pham-Ledard, Emilie Routier, Damien Giacchero, Bertille Bonniaud, Hervé Vallerand, Gilles Quere, C. Stavris, Florian Guisier, François Aubin, Chantal Decroisette, Nathalie Beneton, Ouidad Zehou, Alice Tison, Caroline Robert, Christophe Roge, R. Veillon, Groupe de cancérologie cutanée, François Skowron, Catherine Michel, Divi Cornec, Ioana Carpiuc, Nora Kramkimel, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Ambroise Paré , Assistance Publique - Hôpitaux de Paris (AP - HP), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncologie génito-urinaire, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Eugène Marquis (CRLCC), Hopital d'Aix en Provence, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHI Créteil, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Le Mans (CH Le Mans), CHU Clermont-Ferrand, CHU Rouen, Normandie Université (NU), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Hôpital Foch [Suresnes], Centre Hospitalier de Valence (CH DE VALENCE), Centre hospitalier de Valence, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Henri Mondor, CH Morlaix, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CH, Mantes-La-Jolie, Centre hospitalier Les Chanaux [Mâcon], Hôpital de St Brieuc, Clinique des Cèdres, Service de Médecine Respiratoire [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), CHD Vendee (La Roche Sur Yon), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Lymphocyte B et Auto-immunité (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, autoimmune disease, Inflammatory bowel disease, Autoimmune Diseases, immune checkpoint inhibitors, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Rheumatology, Internal medicine, Psoriasis, Neoplasms, medicine, Immunology and Allergy, Humans, cancer, Progression-free survival, Survival rate, Aged, Retrospective Studies, Autoimmune disease, Aged, 80 and over, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Symptom Flare Up, Progression-Free Survival, 3. Good health, Discontinuation, Survival Rate, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, Rheumatoid arthritis, immune-related adverse events, Female, immunotherapy, business, Immunosuppressive Agents
Abstract: Objective Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune-related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer. Methods A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response. Results The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty-four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression-free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression-free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation. Conclusion Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
Published: 2019

43. The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis

Author: Paul A. Monach, Peter A. Merkel, Ulrich Specks, Kent J. Johnson, John H. Stone, Robert Spiera, Carol A. Langford, Roscoe L. Warner, Philip Seo, Fernando C. Fervenza, Darrell R. Schroeder, Divi Cornec, Cees G. M. Kallenberg, E. William St. Clair, Brian Kabat, Alvise Berti, Mayo Clinic [Rochester], University of Michigan [Ann Arbor], University of Michigan System, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mayo Clinic and Mayo College of Medicine, Rochester, Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland Clinic, University Medical Center Groningen [Groningen] (UMCG), Johns Hopkins University School of Medicine [Baltimore], Hospital for Special Surgery, Duke University Medical Center, Massachusetts General Hospital [Boston], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), and University of Pennsylvania [Philadelphia]
Subjects: Male, 0301 basic medicine, Cytoplasm, Neutrophils, [SDV]Life Sciences [q-bio], Azathioprine, DISEASE-ACTIVITY, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, Proteinase 3, law, immune system diseases, hemic and lymphatic diseases, CYCLOPHOSPHAMIDE, Immunology and Allergy, Longitudinal Studies, skin and connective tissue diseases, ANCA-type, RAVE, B-Lymphocytes, biology, INDUCTION, Remission Induction, MYELOPEROXIDASE, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Cytokines, Drug Therapy, Combination, Female, Rituximab, Vasculitis, Immunosuppressive Agents, ANCA-Associated vasculitis, medicine.drug, medicine.medical_specialty, Cyclophosphamide, Myeloblastin, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Article, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, SYNOVIAL-FLUID, GLOMERULONEPHRITIS, Double-Blind Method, Internal medicine, medicine, Humans, cardiovascular diseases, Interleukin 6, Peroxidase, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, GRANULOMATOSIS, IL-6, business.industry, Interleukin-6, REMISSION, medicine.disease, RHEUMATOID-ARTHRITIS, 030104 developmental biology, biology.protein, business
Abstract: Objective: To investigate serum IL-6 (sIL-6) levels during active disease, complete remission (CR), and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with clinical outcomes.Methods: sIL-6 levels were measured at baseline and longitudinally over 18 months, in 78 patients with AAV enrolled in a randomized controlled trial comparing treatment with either rituximab (RTX) or cyclophosphamide (CYC)/azathioprine (AZA). Outcome variables included baseline clinical features, ANCA specificity, disease activity (active disease versus CR), time to relapse events, B cell repopulation, and ANCA titer increases.Results: At baseline, sIL6 levels were detectable in 81% of patients; 73% (n = 57) of subjects were proteinase 3 (PR3)-ANCA positive, sIL-6 levels were higher in subjects with PR3-ANCAs and positively correlated with their levels (r(s) = 0.36,p 0.05).Conclusion: At baseline, sIL-6 concentrations correlate with PR3-ANCA titers and are associated with specific clinical manifestations of AAV. Baseline sIL6 concentrations do not predict CR at 6 months, but the increase in sIL-6 concentrations during CR is associated with subsequent severe relapse among RTX-treated patients. Further investigation into the mechanistic role of IL6 in AAV might lead to identifying this pathway as a potential therapeutic target in this disease.
Published: 2019

44. Innate B Cells: the Archetype of Protective Immune Cells

Author: Yves Renaudineau, Jacques-Olivier Pers, Marina Boudigou, Laëtitia Le Pottier, Divi Cornec, Nedra Chriti, Sophie Hillion, Alexis Grasseau, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie et Immunothérapie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Laboratoire d'Immunologie et Immunothérapie [Brest]
Subjects: 0301 basic medicine, IgM, medicine.medical_treatment, Regulatory B cells, [SDV]Life Sciences [q-bio], T-Lymphocytes, Population, B-Lymphocyte Subsets, Cell Communication, Biology, Lymphocyte Activation, Immunomodulation, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, Animals, Humans, Innate B cells, education, B cell, 030203 arthritis & rheumatology, education.field_of_study, Effector functions, General Medicine, Marginal zone, Isotype, Immunoglobulin Class Switching, Immunity, Innate, Immunity, Humoral, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Phenotype, Organ Specificity, Immunology, Autoreactivity, Antibody Formation, biology.protein, Cytokines, Antibody
Abstract: International audience; The innate B cell (IBC) population is heterogeneous and involved in the primary immune response. IBC functions include a high ability to produce natural antibodies with IgM isotype, the elimination of apoptotic cells, and a capacity to be cognate help to T cells. Among IBC subsets, B-1 cells and marginal zone B cells are the main producers of IgM, act as rapid immune responders that may relocate to follicular lymphoid and differentiate to cytokine and antibody-secreting cells shortly after infection. IBCs functions are highly dependent on their localization site and the nature of their B cell receptor repertoire, suggesting a high plasticity range of different immune responses. In this review, we will describe the nature and functions of the different innate-like B cell subsets, first in mice and then in humans. Besides this, we will emphasize the strong ability of these cells to undertake different protective functions from the first line of defense against pathogens to the regulatory role of the broader immune response.
Published: 2019

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

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

46. Localized Myofascial Inflammation Revealed by Magnetic Resonance Imaging in Recent-onset Polymyalgia Rheumatica and Effect of Tocilizumab Therapy

Author: Dewi Guellec, Thierry Marhadour, Sandrine Jousse-Joulin, Anaïs Huwart, Valérie Devauchelle-Pensec, Florent Garrigues, Alain Saraux, Divi Cornec, Jean-Patrick Laporte, Département de radiologie [Brest] (DR - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), 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), CIC Brest, and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche
Subjects: musculoskeletal diseases, Male, Shoulder, [SDV]Life Sciences [q-bio], Immunology, Anti-Inflammatory Agents, Pubic symphysis, Antibodies, Monoclonal, Humanized, Lesion, Polymyalgia rheumatica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Fasciitis, Muscle, Skeletal, Myositis, ComputingMilieux_MISCELLANEOUS, Aged, 030203 arthritis & rheumatology, Aged, 80 and over, Inflammation, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Ischial tuberosity, 3. Good health, medicine.anatomical_structure, Treatment Outcome, chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Polymyalgia Rheumatica, Female, medicine.symptom, Nuclear medicine, business, human activities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective.To assess the prevalence of myofascial inflammatory lesions visible by magnetic resonance imaging (MRI) and their changes after tocilizumab (TCZ) therapy in active polymyalgia rheumatica (PMR).Methods.We conducted a posthoc analysis of data from the TENOR study of TCZ monotherapy in PMR. The 18 patients each received TCZ injections at weeks 0, 4, and 8. The shoulder and pelvic girdles were assessed at baseline then at weeks 2 and 12 using T1- and T2- short-tau inversion recovery–weighted MRI. Radiologists blinded to patient data assessed each muscle group for localized myofascial inflammation on baseline, Week 2, and Week 12 MRI. Reproducibility was estimated by having 2 radiologists assess the Week 2 MRI of 13 patients, then computing the κ coefficient.Results.For myofascial lesion detection, intraobserver reproducibility was almost perfect (κ = 0.890) and interobserver reproducibility was substantial (κ = 0.758). At baseline, all patients had at least 1 inflammatory myofascial lesion; sites involved were the shoulder in 10 (71.4%) patients, hip in 13 (86.7%), ischial tuberosity in 9 (60.0%), and pubic symphysis in 12 (80.0%). Sites involved at Week 12 were the shoulder in 8 patients (53.3%), hip in 5 (33.3%), ischial tuberosity in 1, and pubic symphysis in 3 (20.0%). At Week 12, of 103 muscle groups studied in all, 43 (41.7%) had no inflammatory lesions, compared to 33 at baseline (p = 0.002); improvements were noted in 66 (64.1%) muscle groups, worsening in 2 (1.9%), no change in 35 (34.0%; p = 0.034).Conclusion.Localized myofascial inflammatory lesions are common in recent-onset PMR and improve during TCZ therapy. Clinicaltrials.gov (NCT01713842).
Published: 2019

47. Assessment of major salivary gland size in primary Sjögren’s syndrome: comparison between clinical examination and ultrasonography

Author: Laëtitia Le Pottier, Divi Cornec, Pauline Marteau, Thierry Marhadour, Sophie Varache, Yves Gauvin, Maelenn Gouillou, Valérie Devauchelle-Pensec, Dewi Guellec, Guillermo Carvajal Alegria, Sebastian Costa, Jacques-Olivier Pers, Alain Saraux, Yves Renaudineau, Sylvie Boisramé, Sandrine Jousse-Joulin, Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Pathologie, Brest, Service ORL, Department of Odontology, and Laboratoire d'Immunologie et Immunothérapie [Brest]
Subjects: Male, Intraclass correlation, Concordance, salivary glands, [SDV]Life Sciences [q-bio], Submandibular Gland, Physical examination, Severity of Illness Index, Palpation, parotidomegaly, 03 medical and health sciences, 0302 clinical medicine, Cohen's kappa, Rheumatology, stomatognathic system, Major Salivary Gland, medicine, Humans, Parotid Gland, 030212 general & internal medicine, Physical Examination, Ultrasonography, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, ultrasound, Ultrasound, Organ Size, Middle Aged, Parotid gland, stomatognathic diseases, Sjogren's Syndrome, medicine.anatomical_structure, ROC Curve, Sjögren’s syndrome, Female, business, Nuclear medicine, ESSDAI
Abstract: Objective Parotidomegaly is a criterion of the EULAR Primary Sjogren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. Methods Outpatients with primary Sjogren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. Results Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76–1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42–0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. Conclusion Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.
Published: 2019

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

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

49. The pathophysiology of polymyalgia rheumatica, small pieces of a big puzzle

Author: Divi Cornec, Guillermo Carvajal Alegria, Valérie Devauchelle-Pensec, Sara Boukhlal, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), CCSD, Accord Elsevier, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: musculoskeletal diseases, 0301 basic medicine, Aging, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Giant Cell Arteritis, education, Immunology, Human leukocyte antigen, CD8-Positive T-Lymphocytes, Proinflammatory cytokine, Polymyalgia rheumatica, 03 medical and health sciences, 0302 clinical medicine, MESH: B-Lymphocytes, medicine, HLA-DR, Homeostasis, Humans, Immunology and Allergy, In patient, Alleles, MESH: HLA-DRB1 Chains, 030203 arthritis & rheumatology, B-Lymphocytes, B cell, MESH: Humans, Interleukin-6, business.industry, MESH: Alleles, T cell, MESH: Giant Cell Arteritis, medicine.disease, MESH: CD8-Positive T-Lymphocytes, MESH: Interleukin-6, Pathophysiology, 3. Good health, [SDV] Life Sciences [q-bio], Giant cell arteritis, 030104 developmental biology, MESH: Homeostasis, MESH: Polymyalgia Rheumatica, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, HLA-DRB1 Chains
Abstract: International audience; Polymyalgia rheumatica (PMR) is a frequent rheumatic condition among people over 50 years of age. Despite its frequent association with giant cell arteritis (GCA), PMR can be isolated. Its pathophysiology is poorly understood. Nevertheless, many studies are ongoing; 98 studies are currently referenced in ClinicalTrials.org involving several conventional and targeted therapies. In this review, we synthetize the current knowledge about PMR pathophysiology according to genetic and immunogenetic, immunologic, antibody and aging data. Immunogenetic data are mainly related to the HLA system and the association between the HLA-DRB1 and PMR. Few studies are also about immunogenetics of proinflammatory interleukins (i.e. IL-6). The decrease of CD8+Tcells and the strong increase of IL-6 where the main elements of PMR's pathophysiology until the recent years. The disturbance of B cell homeostasis, the search for IL-6 secretion by the innate immune system, the role of aging, are new elements revealed by recent studies. Aging might be a key element to consider as PMR occurs in patients over 50 years of age. Aging may act by the increased susceptibility to infections, by immunological modifications or hormonal disturbances. The role of the cellular infiltration around the joints remains a crucial question. Only a handful of studies described this infiltration. Finally, this review reveals the gaps in available data and suggests new leads and in-depth studies for further research on PMR pathophysiology.
Published: 2020

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

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

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