C. Richez
Centre national de la recherche scientifique
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Featured researches published by C. Richez.
Immunity | 2015
Clément Jacquemin; Nathalie Schmitt; Cécile Contin-Bordes; Yang Liu; Priya Narayanan; Julien Seneschal; Typhanie Maurouard; David S. Dougall; Emily Spence Davizon; Hélène Dumortier; Isabelle Douchet; L. Raffray; C. Richez; Estibaliz Lazaro; Pierre Duffau; M.-E. Truchetet; Liliane Khoryati; P. Mercié; Lionel Couzi; Pierre Merville; Thierry Schaeverbeke; Jean-François Viallard; Jean-Luc Pellegrin; Jean-François Moreau; Sylviane Muller; Sandy Zurawski; Robert L. Coffman; Virginia Pascual; Hideki Ueno; Patrick Blanco
Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) Txa0cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.
Rheumatology | 2016
Thierry Schaeverbeke; M.-E. Truchetet; Marie Kostine; Thomas Barnetche; Bernard Bannwarth; C. Richez
Anti-drug antibodies (ADAbs) develop in up to a third of patients treated with biologic agents, with such immunogenicity being one of the main reasons for the loss of efficacy observed in an important proportion of patients treated with such agents. The appearance of ADAbs has consequences in terms of efficacy and tolerance of the biodrug: the development of ADAbs is associated with a poorer clinical response and with an increased risk of adverse effects. Formation of ADAbs has been observed with all biologic DMARDs, but anti-TNF agent mAbs appear to be the largest contributors, independent of humanization of the antibody. ADAb identification is technically difficult and not standardized, partly explaining important variations between published studies. A variety of factors can influence the risk of ADAb appearance, some of which are linked to the treatment strategy, such as the combination with synthetic DMARDs or the rhythm of administration of the biodrug, whereas other factors are dependent on the patient, such as the level of inflammation at onset or body weight. The detection of these antibodies and/or the dosage of the biologic agent itself could have consequences for the bedside practice of clinicians and should be well understood. This review of the literature proposes an overview of the data published on the subject to help clinicians manage the biodrugs according to these new concepts.
Arthritis & Rheumatism | 2016
M.-E. Truchetet; Béatrice Demoures; Jorge Eduardo Guimaraes; Anne Bertrand; Paôline Laurent; Valérie Jolivel; Isabelle Douchet; Clément Jacquemin; Liliane Khoryati; Pierre Duffau; Estibaliz Lazaro; C. Richez; Julien Seneschal; M.-S. Doutre; Jean-Luc Pellegrin; J. Constans; Thierry Schaeverbeke; P. Blanco; Cécile Contin-Bordes
To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc) by testing the hypothesis that platelets contribute to skin fibrosis via the activation of human dermal microvascular endothelial cells (HDMECs) and subsequent production of profibrotic mediators.
Arthritis & Rheumatism | 2016
M.-E. Truchetet; Béatrice Demoures; Jorge E. Guimaraes; Anne Bertrand; Paôline Laurent; Valérie Jolivel; Isabelle Douchet; Clément Jacquemin; Liliane Khoryati; Pierre Duffau; Estibaliz Lazaro; C. Richez; Julien Seneschal; M.-S. Doutre; Jean-Luc Pellegrin; J. Constans; Thierry Schaeverbeke; P. Blanco; Cécile Contin-Bordes
To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc) by testing the hypothesis that platelets contribute to skin fibrosis via the activation of human dermal microvascular endothelial cells (HDMECs) and subsequent production of profibrotic mediators.
Autoimmunity Reviews | 2017
Guillermo Ruiz-Irastorza; Amaia Ugarte; Cécile Saint-pastou Terrier; Estibaliz Lazaro; Amalur Iza; Lionel Couzi; Ramon Saenz; C. Richez; Sabrina Porta; P. Blanco
OBJECTIVEnTo compare the clinical course of patients with class III, IV and V lupus nephritis (LN) treated at Hospital Universitario Cruces (CC) and at Bordeaux University Hospital (BC).nnnMETHODSnThe Lupus-Cruces nephritis protocol combines pulses of 125mg of methyl-prednisolone with each fortnightly pulse of cyclophosphamide and prednisone ≤30mg/day with tapering over 12-14weeks until 2.5-5mg/day. The BC followed international lupus nephritis guidelines, combining high-dose prednisone and either mycophenolate mofetil or cyclophosphamide, followed by maintenance therapy with low dose prednisone and immunosuppressive drugs. The main outcomes were complete renal remission (CR) and glucocorticoid toxicity.nnnRESULTSn44 patients from BC and 29 from CC were included. The mean maximum prednisone dose was 42.5 (BC) vs. 21mg/day (CC), p<0.001. The average 6-month prednisone dose was 21 (BC) vs. 8.3mg/d (CC), p<0.001.The mean number of methyl-prednisolone pulses was 3 (BC) vs. 9.3 (CC), p<0.001. HCQ was used by 64% (BC) vs. 100% (CC), p<0.001. CR rates were 30% (BC) vs. 69% (CC), p=0.001, and 42% (BC) vs. 86% (CC), p<0.001, at 6 and 12months, respectively. Patients from the CC more frequently achieved CR (adjusted HR 3.8, 95%CI 2.05-7-09). The number of pulses of methyl-prednisolone were associated with CR (adjusted HR 1.09, 95%CI 1.03-1.15). Patients in the CC had a lower risk of GC-related side effects (adjusted HR 0.19, 95%CI 0.04-0.89).nnnCONCLUSIONnThe Lupus-Cruces nephritis protocol improves the outcome of LN. Repeated methyl-prednisolone pulses help reduce the dose of oral glucocorticoids and enhance clinical response.
Arthritis & Rheumatism | 2017
M.-E. Truchetet; Stéphanie Dublanc; Thomas Barnetche; Olivier Vittecoq; Xavier Mariette; C. Richez; P. Blanco; Michael Mahler; Cécile Contin-Bordes; Thierry Schaeverbeke
To assess the prevalence of anti–carbamylated protein (anti‐CarP) antibodies in a French cohort of patients with early arthritis and to investigate their association with clinical features, final diagnosis, prognosis, and comorbidities.
Annals of the Rheumatic Diseases | 2011
Cécile Contin-Bordes; Estibaliz Lazaro; C. Richez; Clément Jacquemin; Olivier Caubet; Isabelle Douchet; Jean-François Viallard; Jean-François Moreau; Jean-Luc Pellegrin; P. Blanco
Objectives Delineation of mechanisms underlying neuropsychiatric systemic lupus erythematosus (NPSLE) and determination of biological markers could guide treatment choice. A study was undertaken to analyse the potential role of activated CD8+ T cells in NPSLE as previously reported in SLE nephritis. Methods Flow cytometric immunophenotyping of blood lymphocytes was performed in 30 patients with NPSLE and 36 healthy individuals. The antigenic specificity of CD8+ T cells was studied using HLA-A0201 tetramers loaded with several myelin-derived peptides. The intracellular level of interferon γ (IFNγ) produced by activated CD8+ T cells was determined by flow cytometry. Results A large increase in circulating activated CD8+ T lymphocytes expressing surface HLA-DR was found in patients with NPSLE without antiphospholipid syndrome (APS) (n=18) compared with patients with APS (n=12) or healthy controls (n=36). IFNγ-secreting myelin-specific CD8+ T cells were detected exclusively in the blood of patients with NPSLE without APS but with white matter lesions. Conclusions These data strongly support the existence of a new immune effector mechanism responsible for CNS involvement in patients with NPSLE and suggest that analysing HLA-DR expression combined with myelin-specific tetramer staining on CD8+ T lymphocytes may be a valuable additional tool for the monitoring of these patients.
Arthritis & Rheumatism | 2017
M.-E. Truchetet; Stéphanie Dublanc; Thomas Barnetche; Olivier Vittecoq; Xavier Mariette; C. Richez; P. Blanco; Michael Mahler; Cécile Contin-Bordes; Thierry Schaeverbeke
To assess the prevalence of anti–carbamylated protein (anti‐CarP) antibodies in a French cohort of patients with early arthritis and to investigate their association with clinical features, final diagnosis, prognosis, and comorbidities.
Annals of the Rheumatic Diseases | 2016
M.-E. Truchetet; B. Demoures; J. Guimaraes; A. Bertrand; Paôline Laurent; Isabelle Douchet; P. Duffau; Estibaliz Lazaro; C. Richez; J. Séneschal; J. Constans; J.-L. Pellegrin; Thierry Schaeverbeke; P. Blanco; Cécile Contin-Bordes
Background Systemic sclerosis (SSc) is a complex systemic autoimmune disease characterized by microvascular dysfunction, immune activation and fibrosis affecting the skin and internal organs (1). Improved characterization of the fibrotic mechanisms involved in SSc is a keystone to developing biomarkers and effective disease-modifying therapies. The activation of endothelial cells (ECs) appears very early in the course of the disease, suggesting that chronic fibroblast activation may be at least partly the result of endothelial dysfunction (1,2). However, the ability of the platelet/EC interaction to induce the secretion of factors directly involved in fibroblast activation and subsequent fibrosis in SSc remains uncertain. Objectives The objective was to provide evidence of a new pathogenic loop implicating activated platelets, microvascular ECs and ECM production in SSc. Methods A total of 203 SSc patients and 30 healthy donors (HDs) were prospectively enrolled between March 2012 and January 2015 at the University Hospital of Bordeaux. Immunohistochemistry and immunofluorescence analysis were performed on skin biopsy specimens from 18 SSc patients and 5 HDs. Serum TSLP levels were measured (ELISA) in the entire cohort. Human dermal microvascular ECs and fibroblasts were purified from normal and SSc patients skin biopsies. Extracellular matrix production by cultured fibroblasts was assessed by RT-qPCR. Results Serum TSLP levels were significantly increased in SSc patients compared to HDs (p=0.0005) and were associated with a higher frequency of vascular damage (p=0.02). The proportion of dermal TSLP-positive cells was increased in the skin biopsies of SSc patients compared to HDs (p=0.0008) and was correlated with skin fibrosis (modified Rodnan skin score) (R=0.059, p=0.01). In SSc dermis, TSLP was mainly expressed by CD31-positive ECs. In vitro, activated platelets induced TSLP production by dermal microvascular ECs in an IL1β-dependent manner. Recombinant TSLP in normal fibroblasts reproducibly induced a pro-fibrotic profile as indicated by a significant increase in the collagen/collagenase ratio (p=0.03). Interestingly, this property was shared by fibroblasts purified from non-fibrotic TSLP-negative SSc skin, but lost with fibroblasts purified from TSLP-positive fibrotic skin. Conclusions Taken together, these results identify dermal microvascular ECs as new contributors to TSLP production in SSc and suggest a potential mechanism by which platelets may profoundly affect the fibrotic process in SSc. References Gabrielli A, et al., N Engl J Med 2009. Pattanaik D, et al., Front Immunol 2015. Disclosure of Interest None declared
RMD Open | 2017
Alessia Alunno; Paul Studenic; Elena Nikiphorou; Petra Balážová; Linda van Nieuwkoop; Sofia Ramiro; Francesco Carubbi; C. Richez; Nele Caeyers; Laure Gossec; Marios Kouloumas
In recent years, the evolution of healthcare challenged the management of people with rheumatic and musculoskeletal diseases (RMDs). From disease-centred care to person-focused care, a holistic approach along with patient empowerment about their disease, improved the physician-patient relationship and allowed to achieve better outcomes with lower healthcare costs. Nevertheless, RMDs may occur from childhood to the old age and to date very few studies have addressed the needs and priorities of young people with RMDs. However, the image of RMDs is still associated with the elderly population. In this regard, the group of young people with arthritis and rheumatism in Europe (PARE) was recently developed within European League Against Rheumatism to represent the voice of the young affected and to carry out projects aiming for a better understanding of these specific aspects. This viewpoint discusses the needs and priorities of young people compared with adult people with RMDs, based on the available literature and on the results of the PARE Youth research project, aiming to identify the next steps of actions that need to be taken to improve the current situation.