Background Accumulation of B cells in synovial lymphoneogenesis (LN) structures could drive antibody-independent synovial inflammation through the development of specific T cell responses or by enhancing cytokine production. This might result in differences in the disease phenotype between patients with and without synovial LN, which might have prognostic interest.
Objectives We analyzed whether synovial lymphoid neogenesis (LN) in rheumatoid arthritis (RA) is associated with specific patterns of inflammatory cytokine expression in synovial tissue (ST) and Synovial fluid (SF), and the potential association of cytokine expression with disease activity and response to therapy.
Methods Paired ST (n=63) and SF (n=44) samples were obtained by arthroscopy from the inflamed knee of RA patients. A second ST sample was obtained after a mean of 8±5 months of treatment in 21 patients who started therapy with TNF-alpha antagonists. ST samples were immunostained for CD3 (T cell), CD20 (B cell), and MECA-79 epitope (high endothelial vessels). Total ST mRNA was extracted and gene expression of CCR7, LT-beta, IL-7, IL-10, IL-17A, IL-21, IL-22, IL-23, TNF-alpha, IL-1b, and IL-6 was measured by quantitative real-time PCR. SF concentration of Th1, Th2, Th17 and proinflammatory cytokines was determined by Quantibody® Human Th17 Array. Clinical and biological data were collected at inclusion and after a median follow-up of 2.4 years.
Results Thirty out of 63 patients (47.6%) had LN, which was associated with a significantly higher expression of ST CCR7 (p=0.009), IL-21 (p=0.009) and IL-23 (p=0.016). LN-positive patients also had significantly higher SF levels of IL-23 (p=0.018) and IL-17F (p=0.028). SF levels of IFN-gamma, TGF-beta1 and IL-21 were higher in LN-positive patients, but the difference did not reached statistical significance. LN-positive patients had significantly higher DAS28 at inclusion (p=0.039). In the group of patients sequentially biopsied before and after anti-TNF-alpha blocker therapy, EULAR good response was only associated with a decrease on IL-10 mRNA expression (p=0.035).
Conclusions RA patients with histological LN exhibit higher expression of Th17/23 related cytokines and higher disease activity as compared to LN-negative patients. Only reduction in IL-10 mRNA expression after anti-TNF-alpha therapy was associated with a better EULAR response.
Disclosure of Interest None Declared
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