循环 CD45RAFoxp3 Treg 细胞可作为预测重症肌无力微小临床表型状态的生物标志物。

Circulating CD45RAFoxp3 Treg cells serve as a biomarker for predicting minimal clinical manifestations status of myasthenia gravis.

机构信息

Department of Neurology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, Guangdong, China.

Department of Neurology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong, China.

出版信息

Life Sci. 2024 Dec 1;358:123162. doi: 10.1016/j.lfs.2024.123162. Epub 2024 Oct 19.

DOI:10.1016/j.lfs.2024.123162

PMID:39433086

Abstract

AIMS

Regulatory T cells (Tregs) are key mediators of the induction of immune tolerance; however, the mechanisms by which they regulate myasthenia gravis (MG) are not fully understood. This study aimed to explore the characteristics of Tregs and their subpopulations in the peripheral blood of patients with minimal clinical manifestations (MM) of MG and identify biomarkers that predict MM-MG for treatment guidance.

MATERIALS AND METHODS

The clinical data of patients with general MG who visited our hospital were retrospectively analyzed. Age- and sex-matched volunteers were selected as healthy controls (HC). Flow cytometry was used to determine the proportion, function, and subpopulations of total Tregs. A correlation analysis was conducted for subpopulation proportions and MG disease severity.

KEY FINDINGS

A total of 27 cases of MM-MG, 40 cases of naїve-MG, and 33 cases of HC were included in this study. The number of total Tregs and the suppressive function of total Tregs were elevated in patients with MM-MG compared to those of patients with naїve-MG. Further analysis revealed that the frequency of CD45RAFoxp3 Tregs (a-Tregs) negatively correlated with quantitative myasthenia gravis (QMG) scores for patients with naїve-MG. In addition, the number of a-Tregs was significantly greater in patients with MM-MG than in patients with naїve-MG, and CD45RAFoxp3 Tregs expressed higher and lower levels of CTLA-4 and CXCR3, respectively.

SIGNIFICANCE

CD45RAFoxp3 Tregs were significantly more abundant and highly expressed surface inhibitory molecules in patients with MM-MG. This profile may serve as a predictive biomarker for MM-MG.

摘要

目的

调节性 T 细胞（Tregs）是诱导免疫耐受的关键介质；然而，它们调节重症肌无力（MG）的机制尚未完全阐明。本研究旨在探讨微小临床症状（MM）MG 患者外周血 Tregs 及其亚群的特征，并鉴定预测 MM-MG 的生物标志物，以指导治疗。

材料和方法

回顾性分析我院就诊的普通型 MG 患者的临床资料。选择年龄和性别匹配的志愿者作为健康对照（HC）。采用流式细胞术检测总 Tregs 的比例、功能和亚群。对亚群比例与 MG 疾病严重程度进行相关性分析。

主要发现

本研究共纳入 27 例 MM-MG、40 例初发 MG 和 33 例 HC。与初发 MG 患者相比，MM-MG 患者总 Tregs 数量和总 Tregs 抑制功能升高。进一步分析发现，初发 MG 患者中 CD45RAFoxp3 Tregs（a-Tregs）的频率与定量重症肌无力（QMG）评分呈负相关。此外，MM-MG 患者的 a-Tregs 数量明显高于初发 MG 患者，且 a-Tregs 表达更高和更低水平的 CTLA-4 和 CXCR3。