Open AccessThe relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: A prospective study
Author(s) -
Klaasen Ruth,
Thurlings Rogier M.,
Wijbrandts Carla A.,
van Kuijk Arno W.,
Baeten Dominique,
Gerlag Danielle M.,
Tak Paul P.
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24913
Subject(s) - medicine , rheumatoid arthritis , lymphocyte , infliximab , psoriatic arthritis , arthritis , tumor necrosis factor alpha , immunology , biomarker , etanercept , synovial membrane , gastroenterology , chemistry , biochemistry
Objective Some patients with rheumatoid arthritis (RA) exhibit lymphocyte aggregates in the synovium. This study was undertaken to address whether the presence of lymphocyte aggregates before treatment could serve as a biomarker for the clinical response to tumor necrosis factor (TNF) blockade, and to confirm whether the aggregation of synovial lymphocytes is reversible after anti‐TNF treatment. Methods Synovial tissue biopsy samples were obtained from 97 patients with active RA before the initiation of infliximab treatment. Lymphocyte aggregates in the synovial tissue were counted and also graded for size. Logistic regression analysis was performed to identify whether the presence of lymphocyte aggregates could be a predictor of the clinical response at week 16. Furthermore, the effects of TNF blockade on lymphocyte aggregates were compared between patients with RA and patients with psoriatic arthritis (PsA). Results Fifty‐seven percent of RA synovial tissue samples contained lymphocyte aggregates, and 32% of the patients had large aggregates. Aggregates were found in 67% of clinical responders compared with 38% of nonresponders. The presence of aggregates at baseline was a highly significant predictor of the clinical response to anti‐TNF treatment (R 2 = 0.10, P = 0.008). Positivity for lymphocyte aggregates increased the power to predict the clinical response (R 2 = 0.29), when analyzed in a prediction model that included baseline disease activity evaluated by the Disease Activity Score in 28 joints, anti–cyclic citrullinated peptide antibody positivity, and synovial TNFα expression. There was a reduction in lymphocyte aggregates after anti‐TNF antibody therapy in both RA and PsA. Conclusion RA patients with synovial lymphocyte aggregates have, on average, a better response to infliximab treatment than those with only diffuse leukocyte infiltration. Moreover, the aggregation of synovial lymphocytes is reversible after anti‐TNF antibody treatment.