CCR4 predicts the efficacy of abatacept in rheumatoid arthritis patients through the estimation of Th17 and Treg cell abundance

Abstract

ABSTRACT Objectives Predicting the efficacy of biological disease–modifying antirheumatic drugs is challenging. In this study, we aimed to explore markers that predict the efficacy of abatacept in rheumatoid arthritis (RA) patients. Methods Thirty RA patients receiving abatacept were recruited, and peripheral blood mononuclear cells from the participants were subjected to DNA microarray analysis. The expression of CC chemokine receptor 4 (CCR4), which was selected by the result of DNA microarray, was determined by flow cytometry in 16 newly diagnosed treatment-naïve RA patients. CCR4 expression on each helper T-cell subset was also measured. Results CCR4 was upregulated in the abatacept responder. The expression levels of CCR4 were significantly correlated with the improvement of the Clinical Disease Activity Index. CCR4 expression was predominantly observed in CD4+ T cells in peripheral blood mononuclear cells. The percentage of CCR4-expressing CD4+ T cells was significantly higher in RA patients than in healthy individuals. Interestingly, Th17 and Treg cells expressed high levels of CCR4 compared to non-Th17-related helper T cells. Conclusions CCR4 is a Th17- and Treg-related gene, and the high CCR4 expression in peripheral blood samples may predict the efficacy of abatacept in RA.