Aberrant Dendritic Cell Subsets in Patients with Myasthenia Gravis and Related Clinical Features.

IF 2.2 4区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuroimmunomodulation Pub Date : 2023-01-01 Epub Date: 2023-02-13 DOI:10.1159/000529626

Yan Song, Chunye Xing, Tianyang Lu, Chen Liu, Wei Wang, Shaoqiang Wang, Xungang Feng, Jianzhong Bi, Qian Wang, Chao Lai

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Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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肌萎缩症患者树突状细胞亚群异常及相关临床特征

导言：树突状细胞（DCs）在重症肌无力（MG）的发病机制中起着关键作用，近年来已开发出一系列基于DCs的重症肌无力实验策略。然而，以往的研究很少涉及不同DC亚群在重症肌无力发病机制中的明确作用。本研究旨在探讨MG患者体内三大DC亚群，即类浆细胞DC（pDCs）（CD303阳性）和传统DC（cDCs）的两个不同亚群，即CD1c+ cDCs和CD141+ cDCs的水平，并分析相关临床特征：2016年1月至2020年12月，研究纳入了160名新确诊的MG患者和匹配的健康对照组（n = 160），并收集了他们的临床数据。收集MG患者治疗前和对照组的血液样本进行流式细胞术分析。共有14个MG胸腺瘤、24个对照组胸腺瘤和3个胸腺囊肿被用于免疫染色DC亚群：流式细胞术分析显示，MG 患者的循环 pDCs、CD1c+ cDCs 和 CD141+ cDCs 的频率明显高于健康对照组（均为 p <0.001）。与晚发型 MG 患者（≥50 岁）相比，早发型 MG 患者（<50 岁）循环 pDCs 的频率较低，但循环 CD1c+ cDCs 的频率较高（分别为 p = 0.014 和 p = 0.025）。循环 pDCs 的频率与晚发型 MG 患者的临床严重程度呈正相关（r = 0.613，p < 0.001）。根据世界卫生组织的分类，64.3%（9/14）的 MG 胸腺瘤属于 B2 型，高于对照组胸腺瘤（33.3%，8/24）（p = 0.019）。就 B2 型胸腺瘤而言，MG 胸腺瘤中的 pDCs 明显多于对照组，但 CD1c+ cDCs 却少于对照组：结论：MG 患者中异常 pDCs、CD1c+ cDCs 和 CD141+ cDCs 的分布显示出与年龄和胸腺瘤相关的差异，这可能是免疫耐受受损并导致 MG 发病的原因之一。

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来源期刊

Neuroimmunomodulation 医学-免疫学

CiteScore

3.60

自引率

4.20%

发文量

审稿时长

>12 weeks

期刊介绍： The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.