Rheumatoid Arthritis: Richez C

Moiton MP, Richez C, Dumoulin C, Mehsen N, Dehais J, Schaeverbeke T. · No affiliation provided · Clin Microbiol Infect. · Pubmed #17121619 No free full text.

Abstract: There is increasing interest concerning the possible impact of anti-tumour necrosis factor (TNF)-alpha therapeutic agents on the emergence of infections. However, these agents do not seem to increase the incidence of adverse infectious events significantly. Published observations concern mostly infections of the urinary and upper respiratory tracts that develop in the setting of co-morbidities, such as anterior or concomitant immunosuppressive treatment. Infliximab appears to increase the risk of tuberculosis, but this effect has not been observed with other anti-TNF-alpha agents. To better characterise the adverse infectious effects associated with these agents, physicians should be encouraged to notify the microbiological data relating to all cases.

Gonnet-Gracia C, Barnetche T, Richez C, Blanco P, Dehais J, Schaeverbeke T. · Department of Rheumatology, University Hospital Pellegrin, Bordeaux Cedex, France. · Clin Exp Rheumatol. · Pubmed #18578960 No free full text.

Abstract: OBJECTIVE: To investigate autoantibody induction in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a cohort of French patients treated with TNF-alpha blockers. METHODS: We tested the serum of patients for antinuclear antibodies (ANA), anti-DNA antibodies and C4 complement at baseline, and for each infusion for infliximab, and at month 3, 6 and 12 for etanercept. We looked for all signs suggesting a drug-induced lupus. We tried to correlate ANA and anti-DNA development with various clinical data, especially the response to treatment. RESULTS: 229 patients were included in the study. 159 were treated with infliximab (98 RA and 61 AS) and 125 with etanercept (116 RA and 9 AS). In the infliximab group, 43.6% of RA patients and 27.1% of AS had significant levels of ANA at baseline. This proportion increased during the follow up to 73% in RA patients and 52% in AS patients. The proportion of patients positive for anti-DNA antibodies increased from 0% to 9.5% in RA group, and from 0% to 2% in AS group. In the etanercept group, 58.5% of these patients had significant levels of ANA at baseline; this proportion raised to 63.3% in patients previously treated with infliximab, and fell to 20.6% in the patients who never received TNF-alpha blockers. No significant variation of ANA, anti-DNA and C4 levels was observed in the etanercept group. Only three patients developed clinical manifestations (chilblain lupus) possibly related to these auto-antibodies, two with infliximab and one with etanercept. CONCLUSION: The ANA induction was only observed under infliximab therapy. Thus, ANA induction seems not to be a therapeutic class effect. This difference between infliximab and etanercept treatment may be the consequence of differential capacity of a monoclonal antibody and a soluble receptor in inducing apoptotic cell death of the cells expressing TNF on their membrane.

Richez C, Schaeverbeke T, Dumoulin C, Dehais J, Moreau JF, Blanco P. · Département de Rhumatologie, CHU Bordeaux,Place Amélie Raba-Léon, 33076 Bordeaux, France. · Arthritis Res Ther. · Pubmed #19563672 links to  free full text

Abstract: INTRODUCTION: The objective of our study was to identify the significance of the subtypes of dendritic cell (DC), specifically myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab. METHODS: Circulating mDC and pDC levels were evaluated by flow cytometry in RA patients (n = 61) and healthy volunteers (n = 30). In RA patients, these levels were measured before and during infliximab therapy. Their counts were correlated to RA disease activity markers and anti-nuclear antibody occurrence. IFNalpha production was measured by ELISA in serum of RA patients and, in vitro, in supernatant of peripheral blood mononuclear cells stimulated by influenza virus in the presence or absence of infliximab. Statistical evaluations were based on Mann-Whitney tests or Wilcoxon's signed-rank tests. RESULTS: RA patients with active disease were characterized by a baseline decrease in both circulating pDCs and mDCs. Disease activity markers inversely correlated only with mDC level. This level increased in RA patients responsive to infliximab therapy, to reach the level observed in controls. Conversely, anti-nuclear antibody appearance during infliximab therapy correlated inversely with pDC level and was associated with increased serum IFNalpha level and circulating plasma cells number. In vitro studies revealed that infliximab kept pDCs in an IFNalpha secreting state upon viral stimulation allowing differentiation of B cells into anti-nuclear antibody-secreting plasma cells. CONCLUSIONS: This study reveals two distinct roles for pDC and mDC in RA. Circulating mDCs mainly contribute to RA activity, whereas pDCs seem to be involved in appearance of anti-nuclear antibodies under infliximab therapy through the ability of this drug to keep pDCs in an IFNalpha secreting state.

Rooryck C, Barnetche T, Richez C, Laleye A, Arveiler B, Schaeverbeke T. · Laboratoire de Génétique Humaine, Université Victor Segalen Bordeaux, Bordeaux Cedex, France. · Clin Exp Rheumatol. · Pubmed #18565259 No free full text.

Abstract: OBJECTIVE: Anti-TNF-alpha therapies are widely used in rheumatoid arthritis (RA) patients. Despite their clearly proven efficacy, some discrepancies were observed in the treatment response with 40% of non-responder patients. The aim of this study is to determine whether two functional single-nucleotide polymorphisms, V212F in the FCGR3A, and M196R in the TNFRSF1B genes correlate with rheumatoid arthritis susceptibility and response to anti-TNF-alpha therapy. METHODS: The population study was composed of a French cohort of 78 RA patients and 70 healthy controls. Allele and genotype frequencies were compared between patients and controls, according to their response to infliximab therapy, using the American College of Rheumatology (ACR) response criteria. RESULTS: No association was found between these two SNPs and RA susceptibility. A significant correlation was found between 196R allele carriers and low response to infliximab therapy. CONCLUSION: This is the first report of a statistically significant association between the TNFRSF1B-M196R SNP and response to infliximab in a French cohort. Larger studies are needed to confirm the relevance of this association.

Richez C, Blanco P, Lagueny A, Schaeverbeke T, Dehais J. · Service de Rhumatologie, Groupe Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux, France. · Neurology. · Pubmed #15851749 No free full text.

Abstract: Tumor necrosis factor-alpha (TauNuFalpha) blockers are effective in the treatment of inflammatory arthritis but can induce autoimmune disorders including multiple sclerosis. Described are two patients who developed chronic inflammatory demyelinating polyneuropathy after initiation of anti-TNFalpha treatment.

Richez C, Blanco P, Gin H, Schaeverbeke T. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #17181936 No free full text.

This publication has no abstract.

Richez C, Dumoulin C, Schaeverbeke T. · No affiliation provided · J Rheumatol. · Pubmed #15801042 links to  free full text

This publication has no abstract.