Department of Neurology, The Second Hospital of Shandong University, Jinan, China.
Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, China.
Neuroimmunomodulation. 2023;30(1):69-80. doi: 10.1159/000529626. Epub 2023 Feb 13.
Dendritic cells (DCs) play critical roles in the pathogenesis of myasthenia gravis (MG), and a series of DC-based experimental strategies for MG have recently been developed. However, the definite roles of different DC subsets in the mechanism of MG have scarcely been covered by previous studies. The present study aimed to investigate the levels of three main DC subsets, plasmacytoid DCs (pDCs) (CD303 positive) and two distinct subsets of conventional DCs (cDCs), namely CD1c+ cDCs and CD141+ cDCs, in MG patients and analyze related clinical features.
From January 2016 to December 2020, 160 newly diagnosed MG patients and matched healthy controls (n = 160) were included in the study, and their clinical data were collected. The blood samples from MG patients before treatment and controls were collected for flow cytometry analysis. A total of 14 MG thymoma, 24 control thymoma, and 3 thymic cysts were used to immunostain the DC subsets.
The flow cytometry analysis showed a significantly higher frequency of circulating pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients than in healthy controls (p < 0.001 for all). Patients with early-onset MG (<50 years old) had a lower frequency of circulating pDCs but a higher frequency of circulating CD1c+ cDCs than those with late-onset MG (≥50 years old) (p = 0.014 and p = 0.025, respectively). The frequency of circulating pDCs was positively associated with the clinical severity of late-onset MG patients (r = 0.613, p < 0.001). 64.3% (9/14) of MG thymoma is of type B2 under the World Health Organization classification, which is higher than that in control thymoma (33.3%, 8/24) (p = 0.019). For type B2 thymoma, there were significantly more pDCs but fewer CD1c+ cDCs in MG thymoma than in the controls.
The distribution of aberrant pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients displayed age- and thymoma-related differences, which may contribute to the impaired immune tolerance and lead to the onset of MG.
树突状细胞（DCs）在重症肌无力（MG）发病机制中发挥关键作用，最近已经开发出一系列基于 DC 的 MG 实验策略。然而，之前的研究几乎没有涉及不同 DC 亚群在 MG 发病机制中的明确作用。本研究旨在探讨 MG 患者中三种主要 DC 亚群（浆细胞样 DCs（pDCs）（CD303 阳性）和两种不同的经典 DC 亚群（cDCs），即 CD1c+ cDCs 和 CD141+ cDCs）的水平，并分析相关的临床特征。
从 2016 年 1 月至 2020 年 12 月，纳入 160 例新诊断的 MG 患者和 160 例匹配的健康对照者（n=160），并收集其临床资料。MG 患者治疗前和对照组的血样用于流式细胞术分析。共对 14 例 MG 胸腺瘤、24 例对照胸腺瘤和 3 例胸腺囊肿进行免疫组化染色以检测 DC 亚群。
流式细胞术分析显示，MG 患者外周血循环 pDCs、CD1c+ cDCs 和 CD141+ cDCs 的频率明显高于健康对照组（均 p < 0.001）。早发性 MG（<50 岁）患者外周血循环 pDCs 的频率较低，但循环 CD1c+ cDCs 的频率较高（p=0.014 和 p=0.025）。循环 pDCs 的频率与晚发性 MG 患者的临床严重程度呈正相关（r=0.613，p < 0.001）。世界卫生组织分类中，64.3%（9/14）的 MG 胸腺瘤为 B2 型，高于对照组的 33.3%（8/24）（p=0.019）。对于 B2 型胸腺瘤，MG 胸腺瘤中的 pDCs 明显多于 CD1c+ cDCs，而对照组则相反。
MG 患者中异常 pDCs、CD1c+ cDCs 和 CD141+ cDCs 的分布存在年龄和胸腺瘤相关差异，这可能导致免疫耐受受损，并导致 MG 的发病。
