Fukuyo Shunsuke, Nakayamada Shingo, Iwata Shigeru, Kubo Satoshi, Saito Kazuyoshi, Tanaka Yoshiya
The First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
Clin Exp Rheumatol. 2017 Jul-Aug;35(4):562-570. Epub 2017 Apr 27.
The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT.
We analysed the peripheral T cell phenotype of 34 RA patients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated.
RA patients showed an increase in the proportion of CD28- cells among CD4+ cells, which was significantly high in patients who had not achieved remission after ABT therapy. The proportions of CD4+CXCR5+ T follicular helper-like (Tfh-like) cells increased in RA patients compared to healthy donors. The proportions of Tfh-like cells among CD4+CD28+ cells were significantly higher than those among CD4+CD28- cells. The proportion of Tfh-like cells was higher in anti-cyclic citrullinated peptide antibody (ACPA)-positive patients. By contrast, the proportions of CD4+CXCR3+ T helper 1-like (Th1-like) cells and effector memory phase T cells among CD4+CD28- cells were significantly higher than those among CD4+CD28+ cells, and the proportion of these cells did not correlate with disease activity. After ABT therapy, the proportion of Tfh-like cells among CD4+CD28+ cells was significantly reduced.
These results imply that CD4+ CD28+ Tfh-like cells could possibly be the targets of ABT. Conversely, CD4+ CD28- cells may be a potential predictor of treatment resistance.
在类风湿关节炎（RA）病例中，阿巴西普（ABT）靶向的T细胞特征仍不清楚。本研究的目的是确定T细胞的致病性以及ABT治疗效果的预测指标。
我们通过流式细胞术分析了34例RA患者的外周血T细胞表型。评估了CD4⁺T细胞表型与临床疾病活动度的相关性，以及基线时和ABT治疗24周后CD4⁺T细胞亚群的变化。
RA患者CD4⁺细胞中CD28⁻细胞的比例增加，在ABT治疗后未达到缓解的患者中这一比例显著升高。与健康供体相比，RA患者中CD4⁺CXCR5⁺滤泡辅助性T细胞样（Tfh样）细胞的比例增加。CD4⁺CD28⁺细胞中Tfh样细胞的比例显著高于CD4⁺CD28⁻细胞中的比例。抗环瓜氨酸肽抗体（ACPA）阳性患者中Tfh样细胞的比例更高。相比之下，CD4⁺CD28⁻细胞中CD4⁺CXCR3⁺辅助性T细胞1样（Th1样）细胞和效应记忆期T细胞的比例显著高于CD4⁺CD28⁺细胞中的比例，且这些细胞的比例与疾病活动度无关。ABT治疗后，CD4⁺CD28⁺细胞中Tfh样细胞的比例显著降低。
这些结果表明，CD4⁺CD28⁺Tfh样细胞可能是ABT的作用靶点。相反，CD4⁺CD28⁻细胞可能是治疗抵抗的潜在预测指标。
