BACKGROUND Ankylosing spondylitis (AS) is a chronic autoimmune disease that involves the imbalance of peripheral tolerance possibly caused by the negative signal of activated T cells. The polymorphisms in the human protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene have been pointed out to be related to the pathogenesis of AS, but conclusions over this issue remain contradictory. We attempted to give a more precise conclusion about the effects of PTPN22 polymorphisms on AS risk by means of a meta-analysis. MATERIAL AND METHODS PubMed, Embase, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies published in the English or Chinese language. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with a fixed- or random-effects model to evaluate the correlation between PTPN22 rs2488457, rs1217414, and rs2476601 polymorphisms and AS susceptibility. Sensitivity analysis was also carried out to detect the stability of the results. RESULTS The present meta-analysis showed a positive correlation of both PTPN22 rs2488457 and rs1217414 polymorphisms with AS risk under CC vs. GG, CC + GC vs. GG, CC vs. GC + GG, allele C vs. allele G (OR=1.39, 95% CI=1.04-1.85, P=0.646; OR=1.29, 95% CI=1.03-1.62, P=0.426; OR=1.26, 95% CI=1.02-1.56, P=0.971; OR=1.20, 95% CI=1.05-1.38, P=0.571), and TT vs. CC and TT vs. CT + CC models (OR=3.83, 95% CI=1.11-13.24, P=0.196; OR=3.83, 95% CI=1.09-13.42, P=0.244), respectively. CONCLUSIONS PTPN22 rs2488457 and rs1217414 polymorphisms may be risk factors for AS occurrence.

BACKGROUND The aim of the current study was to explore the anti-arthritic effect of pinitol via assessing its effect on various inflammatory mediators and its possible mechanism of action. MATERIAL AND METHODS We assessed the anti-arthritic effect of pinitol in a formaldehyde- and CFA-induced arthritic model in Wistar Swiss albino strain rats divided into 6 groups. The rats received different doses of pinitol and indomethacin for 28 days. The arthritic index and body weight were determined at regular intervals, together with hepatic, hematological, and antioxidant parameters. The expression of proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1β) and inflammatory mediators (e.g., COX-2 and VEGF) were also estimated with histopathological evaluation of the joint tissue of rats. A docking study of pinitol with PTPN22 was also carried out. RESULTS The CFA-induced model rats developed redness and nodules in the tail and front paws, and the arthritic control (AC) group rats showed similar symptoms, which were decreased by pinitol administration. The body weight of AC group rats was decreased, while pinitol-treated rats showed considerably increased body weight. Hematological, hepatic, and antioxidant parameters were altered by pinitol in a dose-dependent manner. Pinitol significantly decreased the elevated concentration of proinflammatory cytokines and inflammatory mediators, with improvement in histopathological condition. The docking study suggested that pinitol efficiently interacted with PTPN22 via Arg59, Tyr60, Leu106, and Lys138 by creating close interatomic hydrogen bonds and hydrophobic contacts. CONCLUSIONS Pinitol showed anti-arthritic effects via reduction of proinflammatory cytokines and inflammatory mediators via inhibition of PTPN22.