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高血清 IgA 和活化的 Th17 和 Treg 可预测阿巴西普治疗早期血清阳性类风湿关节炎患者的疗效。

High serum IgA and activated Th17 and Treg predict the efficacy of abatacept in patients with early, seropositive rheumatoid arthritis.

机构信息

Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

出版信息

Clin Rheumatol. 2021 Sep;40(9):3615-3626. doi: 10.1007/s10067-021-05602-0. Epub 2021 Mar 11.

Abstract

OBJECTIVE

To identify the predictive biomarkers for achieving remission with abatacept in patients with seropositive rheumatoid arthritis (RA).

METHODS

We enrolled patients with RA who were treated with abatacept. We compared the baseline laboratory results and longitudinal immune-phenotyping data between patients who achieved remission and those who did not achieve remission at 6 months according to the clinical disease activity index.

RESULTS

One hundred and twenty RA patients were enrolled. In the seropositive patients with early RA (n = 24), high serum IgA levels, anti-citrullinated peptide (CCP) titers, and neutrophil counts before treatment were predictors of remission (area under the curve [AUC], 0.659, 0.741, and 0.704, respectively). Additionally, activated Th17 (aTh17) cells and activated Treg (aTreg) cells before treatment were found to be significantly higher in patients with remission compared to those without remission (2.9% vs 1.1%, P = 0.02; 34.3% vs 17%, P = 0.03, respectively). The measurement of longitudinal cell subpopulation revealed a decrease in the effector CD4 T cell population after abatacept treatment, which correlated with anti-CCP titers and neutrophil counts, and was associated with remission achievement. In seropositive patients with established RA (n = 79), high RF titers and low IFN-γ levels were associated with the good response to abatacept.

CONCLUSION

Our study has shown that serum IgA levels, anti-CCP titer, and neutrophil counts are predictive biomarkers for predicting the response to abatacept in patients with seropositive and early RA and may reflect the inhibition of effector CD4 T cell subpopulations by abatacept. Key Points • Serum IgA levels and neutrophil counts are novel biomarkers for predicting the efficacy of abatacept. • Those may reflect the inhibition of effector CD4 T cell subpopulations by abatacept.

摘要

目的

鉴定出对接受阿巴西普治疗的血清阳性类风湿关节炎(RA)患者达到缓解的预测生物标志物。

方法

我们纳入了接受阿巴西普治疗的 RA 患者。我们根据临床疾病活动指数(clinical disease activity index)比较了 6 个月时达到缓解和未达到缓解的患者的基线实验室结果和纵向免疫表型数据。

结果

共纳入 120 例 RA 患者。在血清阳性早期 RA 患者(n=24)中,治疗前血清 IgA 水平、抗瓜氨酸化肽(anti-citrullinated peptide,CCP)滴度和中性粒细胞计数高是缓解的预测指标(曲线下面积 [area under the curve,AUC]分别为 0.659、0.741 和 0.704)。此外,与未缓解患者相比,缓解患者治疗前的激活 Th17(activated Th17,aTh17)细胞和激活调节性 T 细胞(activated regulatory T cells,aTreg)细胞显著升高(2.9%比 1.1%,P=0.02;34.3%比 17%,P=0.03)。细胞亚群纵向测量显示,阿巴西普治疗后效应性 CD4 T 细胞群减少,与抗 CCP 滴度和中性粒细胞计数相关,与缓解的获得有关。在血清阳性的已确诊 RA 患者(n=79)中,高 RF 滴度和低 IFN-γ 水平与阿巴西普的良好反应相关。

结论

我们的研究表明,血清 IgA 水平、抗 CCP 滴度和中性粒细胞计数是预测血清阳性和早期 RA 患者对阿巴西普反应的预测生物标志物,可能反映了阿巴西普对效应性 CD4 T 细胞亚群的抑制。关键点 • 血清 IgA 水平和中性粒细胞计数是预测阿巴西普疗效的新生物标志物。 • 这些可能反映了阿巴西普对效应性 CD4 T 细胞亚群的抑制。

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