The role of naturally occurring regulatory T cells (Treg) in the control of the immune tolerance of ANCA-associated vasculitis (AAV) has not been well defined. Therefore, we separate the phenotypically heterogeneous Treg cells into different subsets based on the expression of FOXP3 and CD45RA during AAV pathogenesis. Fifty-four AAV patients (38 patients with renal involvement) and 19 healthy controls (HCs) were enrolled in this study. Levels of CD4+T cell subsets and cytokines were detected by flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The diagnostic value for Treg subsets was evaluated by the areas under the receiver operating characteristic curves (AUC). Patients with AAV had lower percentages and numbers of activated Treg cells (aTreg, P = 0.044, P = 0.002), while higher levels of total Treg cells (P = 0.001, P = 0.026) with diminished immunosuppression capacity. The proportions of effector memory T-cell subpopulation (P < 0.001) were increased in AAV patients. Interestingly, the AUC of the aTreg improved significantly the diagnostic potential of AAV. Furthermore, the ratio of Th17/aTreg was significantly increased in active and renal vasculitis patient and positive correlation between Th17/Treg subset ratio and creatinine or BUN. In addition, we found that cytokine IL-2 and IL-4 exhibited a downward while IL-6, IL-10, TNF-α, IFN-γ and IL-17A trend upward in AAV patients. Increase in total Treg levels, along with functional deficiency, and decrease in aTreg cells constitute potential novel biomarkers for AAV. And the ratio of Th17/aTreg might serve as an important tool to recognize and monitor AAV patients with renal involvement and disease remission.

中文翻译：

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活化的调节性T细胞减少和Th17 /活化的Treg细胞失衡标志着肾脏参与了ANCA相关的血管炎。

尚未明确定义天然存在的调节性T细胞（Treg）在控制ANCA相关血管炎（AAV）的免疫耐受中的作用。因此，我们基于AAV发病机理中FOXP3和CD45RA的表达，将表型异质性Treg细胞分为不同的亚组。这项研究纳入了54例AAV患者（38例有肾脏受累的患者）和19例健康对照（HCs）。通过流式细胞仪检测CD4 + T细胞亚群和细胞因子的水平。在共培养实验中测量了Treg的免疫抑制能力。通过接收器工作特性曲线（AUC）下的面积评估Treg子集的诊断值。AAV患者的活化Treg细胞百分比和数量较低（aTreg，P = 0.044，P = 0.002），而较高的总Treg细胞水平（P = 0.001，P = 0.026）却具有较低的免疫抑制能力。AAV患者中效应记忆T细胞亚群的比例增加（P <0.001）。有趣的是，aTreg的AUC显着提高了AAV的诊断潜力。此外，活跃和肾血管炎患者中Th17 / aTreg的比率显着增加，Th17 / Treg子集比率与肌酐或BUN之间呈正相关。此外，我们发现AAV患者的细胞因子IL-2和IL-4呈下降趋势，而IL-6，IL-10，TNF-α，IFN-γ和IL-17A呈上升趋势。总Treg水平的增加，以及功能缺陷，以及aTreg细胞的减少构成了AAV的潜在新生物标记。