Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma
Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma
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胸腺TFH细胞参与重症肌无力合并胸腺瘤的发病机制
DOI：
10.1016/j.expneurol.2014.01.024
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发表时间：
2014-04-01
影响因子：
5.3
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
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作者：
Zhang, Min;Zhou, Yongan;Zhang, Wei
滤泡辅助性CD4+T细胞(TFH)是生发中心(GC)中B细胞帮助的专门提供者。胸腺内GCs的形成是MG患者胸腺的主要特征。TFH细胞参与了许多自身免疫性疾病的发病过程，包括系统性红斑狼疮、类风湿性关节炎和自身免疫性甲状腺疾病。胸腺TFH细胞在MG合并胸腺瘤中的作用尚不清楚。本研究采用免疫组织化学染色、免疫荧光、免疫印迹和实时定量聚合酶链式反应等方法，对胸腺瘤合并眼肌无力(OMG)、全身性MG(GMG)和非MG胸腺TFH细胞表面标志物CXCR5、Bc1-6、ICOS和IL-21进行了分析。我们发现MG的临床严重程度与这四种标记物的高表达有关。事实上，结果显示，与OMG和非MG患者相比，GMG患者胸腺瘤中所有四种标志物的表达都更高。OMG组CXCR5、Bc1-6和ICOS的表达与非MG组比较差异无统计学意义。回归分析显示，GMG患者胸腺CXCR5、BCL-6、ICOS、IL-21水平与定量MG评分(QMGS)呈正相关。此外，我们还发现OMG患者TFH细胞的表达与QMGS之间没有明显的相关性。我们的研究结果表明，胸腺瘤组织中TFH细胞的高表达与MG的临床严重程度有关，提示TFH细胞在MG的发病机制中起一定作用。然而，这些TFH细胞的真正来源仍然不确定，需要进一步研究。(C)2014 Elsevier Inc.保留所有权利。
Follicular helper CD4+T (TFH) cells are the specialized providers of B cell help in germinal centers (GCs). Formation of GCs in thymi is the primary thymi characteristic in MG patients. TFH cells are involved in the pathogenic process of many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and autoimmune thyroid disease. The role thymic TFH cells played in MG with thymoma has not been elucidated. Here, we analyzed surface markers CXCR5, Bc1-6, ICOS and IL-21 on TFH cells in thymus derived from thymoma patients with ocular MG (OMG), generalized MG (GMG) or without MG using immunohistochemical staining, immunofluorescence, western blotting, and real-time PCR analysis. We show that clinical severity of MG is correlated with higher mRNA expression of the four markers. Indeed, results show higher expression of all four markers in thymoma with GMG patients compared with both OMG and non-MG patients. We found no significant difference in the expression of CXCR5, Bc1-6 and ICOS in OMG compared with non-MG patients. Regression analysis shows a positive correlation between thymic CXCR5, BCL-6, ICOS and IL-21 levels and quantitative MG score (QMGS) in GMG patients. In addition, we found no significant correlation between TFH cell expression and QMGS in OMG patients. Our findings show that higher expression of TFH cells in the thymoma is related to the clinical severity of MG and suggests a role in the pathogenesis of MG. However, the real source of these TFH cells is still uncertain and needs further study. (C) 2014 Elsevier Inc All rights reserved.