Synovial lymphoid neogenesis is associated with IL-23 expression and disease activity in rheumatoid arthritis

Abstract

Methods ST samples were obtained by arthroscopy from the inflamed knee of 62 RA patients. A second biopsy was obtained after a mean of 8±5 months of treatment in 21 patients who started TNF blockers. ST samples were immunostained with CD3 (T cell), CD20 (B cell), and MECA-79 (high endothelial vessels). Total ST mRNA was extracted and gene expression of CCR7, LT-beta, IL-7, IL10, IL-17A, IL-21, IL-22, IL-23, TNF-alpha, IL-1b, and IL6 was measured by quantitative real-time PCR. Clinical and biological data were collected at inclusion and after a median follow-up of 2.3 years. Results 28 out of 62 patients (45.2%) had LN, which was associated with a significantly-higher expression of three key molecular markers of LN: CCR7, IL-7 and LT-beta (p<0.037, p<0.038, and p=0.009, respectively). LN-positive patients also had higher IL-23 (p=0.035) and higher DAS28 score, both at inclusion and at the end of followup (p=0.055 and p=0.037, respectively). In the group of patients with ST before and after TNF blocker therapy, EULAR good response was associated with IL-10 reduction (p=0.035). In the entire group, EULAR response correlated with IL-1b expression (P=0.014). Conclusion RA patients with LN were characterized by higher expression of key molecular markers of LN, IL-23 and higher disease activity. A significant reduction in IL-10 expression after therapy with TNF-blockers was associated with good EULAR response.