Objective: To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), we have analysed the clinicopathological correlates of this process and its evolution after anti-TNF-α therapy in a large series of synovial tissues.
Methods: Arthroscopic synovial biopsies from 86 RA patients were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B-cell compartmentalization and PNAd-positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN-positive and negative RA subsets. We also analysed the evolution of LN and its correlation with the clinical course in a subgroup of 24 patients that underwent a second arthroscopic biopsy after anti-TNF-α therapy.
Results: LN was present in 49% RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNF-α agents. During prospective follow-up, the proportion of patients achieving good or moderate EULAR DAS28 responses was significantly lower in LN-positive patients despite a significantly higher use of anti-TNF-α agents. By multivariate logistic regression analysis, LN remained as an independent negative predictor of response to therapy. In the subgroup of patients rebiopsied after anti-TNF-α therapy, reversal of LN features occurred in 56% of the patients and correlated with good clinical responses.
Conclusions: Synovial LN in RA predicts a lower response to therapy. LN features can be reversed after a short period of anti-TNF-α therapy in parallel to good clinical responses.
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