The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: a prospective study.
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 TNFalpha expression. There was a reduction in lymphocyte aggregates after anti-TNF antibody therapy in both RA and PsA.


CONCLUSIONS
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.
Klaasen
Ruth
R
University of Amsterdam, Amsterdam, The Netherlands.
Thurlings
Rogier M
RM
Wijbrandts
Carla A
CA
van Kuijk
Arno W
AW
Baeten
Dominique
D
Gerlag
Danielle M
DM
Tak
Paul P
PP
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D015415:Biomarkers; D001706:Biopsy; D002449:Cell Aggregation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069285:Infliximab; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000473:pathology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab