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IL-35 产生 T 和 B 细胞在乙酰胆碱受体抗体阳性重症肌无力中的作用。

Roles of IL-35-producing T and B cells in anti-acetylcholine receptor antibody-positive myasthenia gravis.

机构信息

Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Department of Neurology, First Affiliated Hospital of Hainan Medical University, Haikou, China.

出版信息

J Clin Neurosci. 2022 Jan;95:75-80. doi: 10.1016/j.jocn.2021.11.020. Epub 2021 Dec 9.

Abstract

BACKGROUND

Interleukin 35 (IL-35) plays an anti-inflammatory in numerous autoimmune diseases. However, the potential roles of IL-35-producing T and B cells and serum IL-35 levels in the pathogenesis of myasthenia gravis (MG) and its association with disease activity in patients with MG remain unclear.

METHODS

The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells among peripheral blood mononuclear cells were determined in 37 patients with anti-acetylcholine receptor (AChR) antibody-positive MG and 35 healthy controls (HCs) by performing a flow cytometry analysis. Serum IL-35 levels in participants were determined using an enzyme-linked immunosorbent assay. Further, the correlations between IL35 levels and disease activity were analysed.

RESULTS

The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells were significantly lower in patients with anti-AChR antibody-positive MG than in HCs (p = 0.001 and p = 0.002, respectively). Furthermore, patients with thymoma and patients with generalized MG had lower percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells than those without thymoma and those with ocular MG (p = 0.001 and p = 0.003; p = 0.008 and p = 0.001, respectively). Interestingly, the suppression of IL-35 secretion correlated negatively with the activities of daily living scores of patients with MG (r = -0.4774, p = 0.0028) and the quantitative MG scores (r = -0.4656, p = 0.0037). The proportions of IL-35-producing T cells and B cells and serum levels of IL-35 increased after treatment.

CONCLUSIONS

IL-35 may represent a potential biomarker for the clinical evaluation of MG.

摘要

背景

白细胞介素 35 (IL-35) 在许多自身免疫性疾病中发挥抗炎作用。然而,IL-35 产生的 T 和 B 细胞以及血清 IL-35 水平在重症肌无力 (MG) 发病机制中的潜在作用及其与 MG 患者疾病活动的关系尚不清楚。

方法

通过流式细胞术分析,测定 37 例抗乙酰胆碱受体 (AChR) 抗体阳性 MG 患者和 35 例健康对照者 (HCs) 外周血单个核细胞中 IL-35 产生的 CD4+CD25+T 细胞和 CD19+B 细胞的百分比。采用酶联免疫吸附试验测定参与者的血清 IL-35 水平。进一步分析了 IL35 水平与疾病活动的相关性。

结果

抗 AChR 抗体阳性 MG 患者 IL-35 产生的 CD4+CD25+T 细胞和 CD19+B 细胞的百分比明显低于 HCs(p=0.001 和 p=0.002)。此外,胸腺瘤患者和全身性 MG 患者的 IL-35 产生的 CD4+CD25+T 细胞和 CD19+B 细胞百分比低于无胸腺瘤和眼肌型 MG 患者(p=0.001 和 p=0.003;p=0.008 和 p=0.001)。有趣的是,IL-35 分泌的抑制与 MG 患者的日常生活活动评分(r=-0.4774,p=0.0028)和定量 MG 评分(r=-0.4656,p=0.0037)呈负相关。治疗后,IL-35 产生的 T 细胞和 B 细胞的比例以及血清 IL-35 水平增加。

结论

IL-35 可能是 MG 临床评估的潜在生物标志物。

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