Presentation: In Active, Early Rheumatoid Arthritis, CXCR4+ T Cells in Peripheral Blood are Up-Regulated, Partly Correlates to Disease Activity and a Potential Predictor of the Response to Methotrexate Treatment (2007)

154 In Active, Early Rheumatoid Arthritis, CXCR4+ T Cells in Peripheral Blood are Up-Regulated, Partly Correlates to Disease Activity and a Potential Predictor of the Response to Methotrexate Treatment

Background: CXCR4 is the unique receptor for the chemokine CXCL12 and their coupling elicits pro-inflammatory actions in rheumatoid arthritis (RA). This ligand - receptor system is involved in lymphocyte migration into and accumulation in the RA joints, lymphoid-tissue-like T-cell (TC) rearrangement within the synovium, chondrocyte release of cartilage-degrading metalloproteinases (MMPs) and neo-angiogenesis of importance for pannus growth.
Objectives: To analyse the peripheral blood TC expression of CXCR4 and lymphocyte activation in relation to clinical aspects of RA compared with healthy controls.
Methods: This RCT study comprised 40 early (< 6 months duration) RA patients, participating in the CIMESTRA study. In RA patients, peripheral blood TC CXCR4 expression was determined by flow cytometry (FCM) prior to methotrexate (MTX) +/- cyclosporine A (CsA) treatment and after 6 and 11 months. In 9 healthy controls it was determined once. Multi-colour FCM was performed using the monoclonal antibodies (MoAbs) against CD3, CD4, CXCR4, and the TC activation markers CD38 or CD69.
Results: “Low responders” (ACR20 or less) to MTX treatment after 11 months could be identified from day one, based on a significantly decreased number of circulating CD3+CD4+CD38+ TCs.
TC CXCR4 expression and RA disease activity (DAS score) were associated at some time points. The CXCR4 median fluorescence intensity (MFI) was significantly higher in healthy controls compared with early RA patients. This finding may reflect undetectable, compartmentalised, or truly down-regulated CXCR4 ikke i results men i conclusion, det er din tolkning. Compared with healthy controls, active, early RA patients had increased total amounts of peripheral blood CD3+CD4+CXCR4+ TCs. CsA had no impact on CXCR4 expression on any TC subset at any time in the study. TC CXCR4 expression and joint erosions were not correlated at any time.
Conclusions: The number of CXCR4+ peripheral blood TCs was up-regulated in early, active RA. Further, the number of CXCR4+ peripheral blood TCs correlated to the DAS score of RA disease activity at some time points, but not to the development of joint erosions. Finally, this is the first study to report that this TC subset is a potential predictor of the response to MTX treatment.
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 I. Hansen, None; T. Ellingsen, None; B.K. Møller, None; J. Krog, None; K. Hørslev-Petersen, None; M.L. Hetland, None; K. Stengaard-Pedersen, None.