Genetic markers in clinical subtypes of juvenile idiopathic arthritis

Poster presentatationInternational audienc

TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis

International audienceObjective: To evaluate the association between several candidate single-nucleotide polymorphisms (SNPs) and responsiveness to rituximab in patients with rheumatoid arthritis (RA). Methods: Sixty-three RA patients were included. Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGF beta 1, TNF-alpha, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22). Results: Forty-four patients were defined as responders and 19 as nonresponders. TGF beta 1 Codon 10 and TGF beta 1 Codon 25 SNPs were both associated with clinical response (probability to respond to treatment with the Codon 10 C/T genotype: OR = 1.6; P = 0.002, and with the Codon 25 G/C genotype: OR = 1.6; P = 0.025). The probability to be a responder when the TGF beta Codon10 C/T and TGF beta Codon 25 G/C genotypes were co-inherited, doubled (OR = 2.6; P = 0.008). Conclusion: The TGF beta 1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome. (C) 2011 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved

Clinical association of mixed connective tissue disease and granulomatosis with polyangiitis: a case report and systematic screening of anti-U1RNP and anti-PR3 auto-antibody double positivity in ten European hospitals

We report here the case of a 50-years-old man treated for mixed connective tissue disease (MCTD) positive for anti-U1 ribonucleoprotein (U1RNP) antibodies who secondarily developed a granulomatosis with polyangiitis (GPA) associated with anti-proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA). We then evaluated the frequency of the association between anti-U1RNP and anti-PR3-ANCA antibodies by a systematic retrospective study in ten European hospitals. Overall, out of 11,921 samples analyzed for both auto-antibodies, 18 cases of anti-U1RNP and anti-PR3-ANCA double positivity were found and only one patient presented with both MCTD and GPA symptoms. Our retrospective analysis indicates that anti-U1RNP and anti-PR3-ANCA antibodies double positivity is infrequent and very rarely associated with both MTCD and GPA. Our observation describes for the first time the coexistence of MTCD and severe GPA in a Caucasian patient. Association of anti-U1RNP and ANCA antibodies was rarely reported in the literature. Eleven cases of MCTD and ANCA vasculitis have been reported to date, with only two cases with anti-PR3-ANCA association, and only one vasculitis. The seven other cases reported in the literature presented with an association of MCTD and microscopic polyangiitis which appears to be a more frequent presentation than MTCD associated with GPA.status: publishe