Wang Lifang, Zhang Yu, Zhu Mingqin, Feng Jiachun, Han Jinming, Zhu Jie, Deng Hui
Department of Neurology, the First Bethune Hospital, Jilin University, Changchun 130021, Jilin Province, China.
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden.
Curr Mol Med. 2019;19(10):739-745. doi: 10.2174/1566524019666190827162615.
Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acetylcholine receptors (AChR) of the skeletal muscles. An imbalance in various T helper (Th) cells, including Th1, Th2, Th17, Th22 and follicular helper T (TFH) cells, has been found associated with immunological disturbances.
In this study, we aim to investigate the role of the Th cells in peripheral blood of MG patients.
A total of 33 MG patients and 34 age matched controls were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque density gradient centrifugation assay. The proportion of TFH cells in PBMC were analyzed using flow-cytometry assay by determining the levels of cellular markers CD4, CXCR5, CD45RO, CD45RA and ICOS and PD-1. The levels of IFN-γ, IL-4, IL-17 and IL-21 in serum were analyzed by Cytometric Bead Array. The serum IL-22 level was analyzed by ELISA.
The frequency of TFH cells in PBMCs was higher than those in healthy subjects and correlated to the severity of MG patients. The levels of pro-inflammatory cytokines IFN-γ, IL-17 and IL-21 were elevated in the serum of MG patients, while there were no significant differences regarding the levels of IL-4 and IL-22 between MG patients and control subjects.
Our findings suggest that Th cells and their cytokines balance of MG patients are involved in the clinical condition or severity of MG disease.
重症肌无力(MG)是一种由针对骨骼肌乙酰胆碱受体(AChR)的抗体介导的自身免疫性疾病。已发现包括Th1、Th2、Th17、Th22和滤泡辅助性T(TFH)细胞在内的各种辅助性T(Th)细胞失衡与免疫紊乱有关。
在本研究中,我们旨在探讨Th细胞在MG患者外周血中的作用。
本研究共纳入33例MG患者和34例年龄匹配的对照。采用Ficoll-Paque密度梯度离心法分离外周血单个核细胞(PBMC)。通过流式细胞术检测PBMC中TFH细胞的比例,测定细胞标志物CD4、CXCR5、CD45RO、CD45RA以及ICOS和PD-1的水平。采用细胞因子微珠阵列分析血清中IFN-γ、IL-4、IL-17和IL-21的水平。采用ELISA法分析血清IL-22水平。
MG患者PBMC中TFH细胞频率高于健康受试者,且与MG患者的病情严重程度相关。MG患者血清中促炎细胞因子IFN-γ、IL-17和IL-21水平升高,而MG患者与对照受试者之间IL-4和IL-22水平无显著差异。
我们的研究结果表明,MG患者的Th细胞及其细胞因子平衡与MG疾病的临床状况或严重程度有关。