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[抗中性粒细胞胞浆髓过氧化物酶抗体相关血管炎患者循环滤泡辅助性T细胞的临床意义]

[The clinical significance of circulating follicular helper T cells in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis].

作者信息

Wang S, Zheng M J, Zhou X L, Liu Y Q, Shuai Z W

机构信息

Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2018 Oct 1;57(10):738-742. doi: 10.3760/cma.j.issn.0578-1426.2018.10.008.

Abstract

To investigate the change of circulating follicular helper T cells (cTfh) in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis (MPO-AAV), and to analyze the relationship between cTfh and disease activity. Thirty-eight untreated MPO-AAV patients (patient group) and thirty-eight healthy volunteers (control group) were enrolled in this study. cTfh and membrane expression of inducible co-stimulator (ICOS) and programmed cell death protein 1 (PD-1) were detected by flow cytometry (FCM). Serum anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA) was measured by ELISA. Disease activity was evaluated by Birmingham vasculitis activity score (BVAS). Compared with those in control group, the proportions of cTfh, ICOS(+)Tfh and PD-1(+) Tfh cells in patient group were significantly higher [(25.9±3.8)% vs. (21.0±5.3)%, <0.001; (1.8±0.8)% vs. (0.8±0.5)%, <0.001 and (10.2±2.8)% vs. (8.2±2.2)%, 0.001, respectively]. Meanwhile, the expression of ICOS and PD-1 on cTfh in patient group was markedly more intensive (59.6±10.0 vs.49.2±6.9, <0.001 and 532.6±104.2 vs. 485.1±73.4, 0.025, respectively). In patient group, the proportion of cTfh was positively correlated with the ratio of ICOS(+)Tfh, the expression of ICOS, the level of MPO-ANCA and BVAS (0.407, 0.011; 0.705, 0.001; 0.737, 0.001 and 0.663, 0.001, respectively). The expression intensity of ICOS on cTfh was positively associated with ICOS(+)Tfh ratio, serum MPO-ANCA and BVAS (0.388, 0.016; 0.645, 0.001 and 0.653, 0.001, respectively). Nevertheless, the expression of PD-1 on cTfh was only positively correlated with the ratio of PD-1(+) Tfh (0.473, 0.003). Enhanced cTfh in patients with MPO-AAV might produce MPO-ANCA, which is related to the aggravation of MPO-AAV. Thus, cTfh and its ICOS could be potentially targeted for the treatment of MPO-AAV.

摘要

探讨抗中性粒细胞胞浆髓过氧化物酶抗体相关性血管炎(MPO-AAV)患者循环滤泡辅助性T细胞(cTfh)的变化,并分析cTfh与疾病活动度之间的关系。本研究纳入了38例未经治疗的MPO-AAV患者(患者组)和38例健康志愿者(对照组)。采用流式细胞术(FCM)检测cTfh及诱导性共刺激分子(ICOS)和程序性细胞死亡蛋白1(PD-1)的膜表达。采用酶联免疫吸附测定(ELISA)检测血清抗中性粒细胞胞浆髓过氧化物酶抗体(MPO-ANCA)。采用伯明翰血管炎活动评分(BVAS)评估疾病活动度。与对照组相比,患者组cTfh、ICOS(+)Tfh和PD-1(+)Tfh细胞比例显著更高[分别为(25.9±3.8)%对(21.0±5.3)%,<0.001;(1.8±0.8)%对(0.8±0.5)%,<0.001;(10.2±2.8)%对(8.2±2.2)%,0.001]。同时,患者组cTfh上ICOS和PD-1的表达明显更强[分别为59.6±10.0对49.2±6.9,<0.001;532.6±104.2对485.1±73.4,0.025]。在患者组中,cTfh比例与ICOS(+)Tfh比例、ICOS表达、MPO-ANCA水平和BVAS呈正相关(分别为0.407,0.011;0.705,0.001;0.737,0.001和0.663,0.001)。cTfh上ICOS的表达强度与ICOS(+)Tfh比例、血清MPO-ANCA和BVAS呈正相关(分别为0.388,0.016;0.645,0.001和0.653,0.001)。然而,cTfh上PD-1的表达仅与PD-1(+)Tfh比例呈正相关(0.473,0.003)。MPO-AAV患者中cTfh增强可能产生MPO-ANCA,这与MPO-AAV的加重有关。因此,cTfh及其ICOS可能是MPO-AAV治疗的潜在靶点。

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