Objective: To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), the clinicopathological correlates of this process and its evolution after anti-tumour necrosis factor (TNF)α therapy in a large series of synovial tissues were analysed.
Methods: Arthroscopic synovial biopsies from 86 patients with RA were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B cell compartmentalisation and peripheral node addressin (PNAd) positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN positive and negative RA subsets. 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-TNFα therapy was also analysed.
Results: LN was present in 49% of RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNFα agents. During prospective follow-up, the proportion of patients achieving good or moderate European League Against Rheumatism (EULAR) 28-joint Disease Activity Score (DAS28) responses was significantly lower in patients who were LN positive despite a significantly higher use of anti-TNFα 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-TNFα 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-TNFα therapy in parallel to good clinical responses.
Statistics from Altmetric.com
Competing interests: None.
Funding: This work was supported by the Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo (FIS 04/1023, 04/1027 and 05/983 to JDC, and 05/60 to JLP) and by a grant from Fundación Española de Reumatología/Abbot Laboratories to JDC. CM was supported by a grant from Hospital Clínic de Barcelona, and EI by the predoctoral programme of the Fondo de Investigación Sanitaria.
Ethics approval: All patients signed an informed consent and the study was approved by the Ethical Committee of the Hospital Clinic of Barcelona.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.