Peripheral blood CD4+CD25+CD127low regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with…

Jun Kikuchi, Misato Hashizume, Yuko Kaneko, Keiko Yoshimoto, Naoshi Nishina, Tsutomu Takeuchi

IntroductionTocilizumab (TCZ), an anti-interleukin-6 receptor antibody, is clinically effective against rheumatoid arthritis (RA), and several reports have indicated how TCZ influences a number of mechanisms underlying RA pathogenesis. However, it is still unclear whether TCZ affects inflammatory cells in peripheral blood and whether any such changes are associated with clinical response. We evaluated associations between proportions of subsets of peripheral immune cells and clinical response in RA patients treated with TCZ.MethodsThirty-nine consecutive RA patients who started to receive TCZ as their first biologic between March 2010 and April 2012 were enrolled. The proportions of several subsets of peripheral cells with their levels of expression of differentiation markers, activation markers, and co-stimulatory molecules were measured sequentially from baseline to Week 52 by flow cytometry analysis.Resultsclinical disease activity index (CDAI) remission was achieved in 53.8% of patients at week 52 of TCZ therapy. The proportions of CD4+CD25+CD127low regulatory T cells (Treg) and HLA-DR+ activated Treg significantly increased with TCZ therapy (P <0.001 and P <0.001, respectively), whereas proportions of CD3+CD4+CXCR3¿CCR6+CD161+ T helper 17 cells did not change over the 52 weeks. The proportions of CD20+CD27+ memory B cells, HLA-DR+CD14+ and CD69+CD14+ activated monocytes, and CD16+CD14+ monocytes significantly decreased (P <0.001, P <0.001, P <0.001, and P <0.001, respectively). Among them, only the change in Treg was inversely correlated with the change in CDAI (rho¿=¿¿ 0.40, P¿=¿0.011). The most dynamic increase in Treg was observed in the CDAI remission group (P <0.001).ConclusionThis study demonstrates that TCZ affected proportions of circulating immune cells in RA patients. The proportion of Treg among CD4+ cells correlated well with clinical response.