Kikuchi Jun, Hashizume Misato, Kaneko Yuko, Yoshimoto Keiko, Nishina Naoshi, Takeuchi Tsutomu
Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co, Ltd 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
Arthritis Res Ther. 2015 Jan 21;17(1):10. doi: 10.1186/s13075-015-0526-4.
Tocilizumab (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 patients with RA treated with TCZ.
Thirty-nine consecutive patients with RA 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 costimulatory molecules were measured sequentially from baseline to week 52 by flow cytometry analysis.
Clinical Disease Activity Index (CDAI) remission was achieved in 53.8% of patients at week 52 of TCZ therapy. The proportions of CD4(+)CD25(+)CD127(low) regulatory T cells (Treg) and HLA-DR(+) activated Treg cells 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 cells was inversely correlated with the change in CDAI score (ρ = -0.40, P = 0.011). The most dynamic increase in Treg cells was observed in the CDAI remission group (P < 0.001).
This study demonstrates that TCZ affected proportions of circulating immune cells in patients with RA. The proportion of Treg cells among CD4(+) cells correlated well with clinical response.
托珠单抗（TCZ）是一种抗白细胞介素-6受体抗体，对类风湿关节炎（RA）具有临床疗效，多项报告指出了TCZ对RA发病机制中多种机制的影响。然而，TCZ是否会影响外周血中的炎症细胞以及这些变化是否与临床反应相关仍不清楚。我们评估了接受TCZ治疗的RA患者外周免疫细胞亚群比例与临床反应之间的关联。
纳入了39例在2010年3月至2012年4月期间开始接受TCZ作为首个生物制剂治疗的连续性RA患者。通过流式细胞术分析，从基线到第52周依次测量外周细胞几个亚群及其分化标志物、激活标志物和共刺激分子表达水平的比例。
在TCZ治疗第52周时，53.8%的患者实现了临床疾病活动指数（CDAI）缓解。随着TCZ治疗，CD4(+)CD25(+)CD127(low)调节性T细胞（Treg）和HLA-DR(+)活化Treg细胞的比例显著增加（分别为P < 0.001和P < 0.001），而CD3(+)CD4(+)CXCR3(-)CCR6(+)CD161(+)辅助性T细胞17在52周内比例未改变。CD20(+)CD27(+)记忆B细胞、HLA-DR(+)CD14(+)和CD69(+)CD14(+)活化单核细胞以及CD16(+)CD14(+)单核细胞的比例显著降低（分别为P < 0.001、P < 0.001、P < 0.001和P < 0.001）。其中，只有Treg细胞的变化与CDAI评分的变化呈负相关（ρ = -0.40，P = 0.011）。在CDAI缓解组中观察到Treg细胞最显著增加（P < 0.001）。
本研究表明TCZ影响RA患者循环免疫细胞的比例。CD4(+)细胞中Treg细胞的比例与临床反应密切相关。
Zotero 插件