Rheumatoid Arthritis: Blanco P

Bloch-Michel C, Viallard JF, Blanco P, Liferman F, Neau D, Moreau JF, Baillet L, Etienne G, Longy-Boursier M, Pellegrin JL. · Service de médecine interne et maladies infectieuses, hôpital du Haut-Lévêque, 5, avenue Magellan, 33604 Pessac, France. · Rev Med Interne. · Pubmed #14550517 No free full text.

Abstract: PURPOSE: Common variable immunodeficiency (CVID) is an immune defect characterized by primary hypogammaglobulinemia. Most of the time, clinical manifestations that reveal CVID are recurrent bacterial infections, but auto-immune or granulomatous events may occur. METHODS: This retrospective study was conducted on 17 patients fulfilling the classical CVID definition. Lymphocyte activation level was evaluated in 12 patients through HLA-DR expression on lymphocytes subsets. RESULTS: This study includes 17 patients, 7 men and 10 women. The mean age at the first clinical manifestation is 23 years and the mean age at diagnosis is 39 years. Recurrent upper and lower bacterial respiratory tract infections are common to all patients. Abdominal infection due to Mycobacterium avium-intracellulare complex is found in one patient. Digestive events are dominated by chronic diarrhea caused by giardiasis, nodular lymphoid hyperplasia or villous atrophy. Seven patients developed auto-immune conditions (insulin dependent diabetes, idiopathic thrombocytopenic purpura (ITP), rheumatoid arthritis) and 7 patients have a splenomegaly. Non caseating granulomas in the spleen or in lymph node biopsies are found in 3 patients. Ten patients have a T lymphopenia, 2 have a B lymphopenia, 5 have a CD4/CD8 ratio <1, and 6 have T CD4(+) lymphocytes <400/mm(3). The study of HLA-DR expression on lymphocytes subsets shows that 7/12 patients have activated T CD4(+) and/or CD8(+) cells and these patients have auto-immune or tumoral manifestations. The other 5 patients do not have activated T lymphocytes but present with infectious events only. CONCLUSIONS: Our study allows the separation of patients with CVID according to their T lymphocytes activation level. A patient's classification is necessary to define homogeneous groups of patients to perform genetic and functional studies which will probably reveal heterogeneous molecular abnormalities.

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.

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.

Youssef J, Lazaro E, Blanco P, Viallard JF. · No affiliation provided · J Rheumatol. · Pubmed #19143047 No free full text.

This publication has no abstract.

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.