Decreased expression of circulating Aire and increased Tfh/Tfr cells in myasthenia gravis patients
Decreased expression of circulating Aire and increased Tfh/Tfr cells in myasthenia gravis patients
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重症肌无力患者循环 Aire 表达减少和 Tfh/Tfr 细胞增加
DOI：
10.1042/bsr20180096
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发表时间：
2018-12-21
影响因子：
4
通讯作者：
Li, Zhuyi
中科院分区：
文献类型：
--
作者：
Zhao, Sijia;Ding, Jiaqi;Li, Zhuyi
重症肌无力(MG)是由抗突触后膜蛋白抗体(Ab)引起的一种罕见的自身免疫性疾病。多数报道探讨了胸腺组织中自身免疫调节基因(Aire)在MG发病机制中的作用。到目前为止，Aire在人外周血细胞中的表达(我们在下文中称之为循环Aire表达)尚未见报道。在此，我们探讨了Aire在MG患者外周血、循环T滤泡辅助细胞(CTfh)和T滤泡调节细胞(CTfr)中的表达。本研究发现泛发性MG(GMG)患者的乙酰胆碱受体(AChR)抗体水平高于眼部MG(OMG)。与对照组相比，Aire在MG患者中的表达降低，尤其在GMG患者中更为明显。Tfh/TfR比值在GMG组较高，OMG组次之，CG组最低。以上差异均有统计学意义。循环血中Aire的表达与Tfh/Tfr比值呈负相关，与MG病情严重程度呈负相关。同时，Tfh/TfR比值与MG病情严重程度呈正相关。然而，在我们的研究中，MG的亚组年龄与Aire水平之间没有明显的关系。总之，这些发现提示循环Aire可能在cTfh/cTfr细胞失衡中起作用，并参与MG的发病。
Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells (we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T-follicular helper (cTfh) and T-follicular regulatory (cTfr) cells in MG patients. In our research, we found that the acetylcholine receptor (AChR) Ab level is higher in generalized MG (GMG) than that in ocular MG (OMG). Compared with the control group (CG), lower expression of Aire was found in MG patients, especially in GMG. The ratio of Tfh/Tfr was higher in GMG patients, and then in the OMG patients, and lowest in CG. All these differences above were statistically significant. Negative relation was discovered between expression of Aire in circulating blood and ratio of Tfh/Tfr, so did it exist between Aire expression and the severity of MG. Meanwhile, positive relation was discovered between ratio of Tfh/Tfr and the severity of MG. However, no significant relation was manifested in our study between the subset age of MG and Aire level. Overall, these findings imply circulating Aire might play a role in the imbalance of cTfh and cTfr cells and participate in the pathogenesis of MG.