儿童重症肌无力患者胸腺细胞异常增生相关因素分析

Associated Factors of Thymic Hyperplasia in Children with Myasthenia Gravis

目的探讨儿童重症肌无力(myasthenia gravis,MG)患者胸腺细胞异常增生的机制。方法取单纯胸腺增生型MG患者胸腺组织,经病理组织切片、苏木精-伊红(HE)染色和免疫组化染色,观察患者胸腺组织的结构和分子表达特点;通过提取胸腺组织RNA和基因芯片检查,分析与胸腺异常增生相关的细胞因子、膜分子及信号通路表达。结果 MG患者胸腺细胞显著增生,CD3分子呈强阳性表达,HLA-DR分子在髓质表达更明显。多种细胞因子、膜分子和信号分子表达存在异常,其中BCL2、CCL22、CCL25、CCL3、CCR7、CCR9在儿童MG患者胸腺显著增高;而CCL2、CSF3、CSF3R、CX3CL1、CXCL9、IL-1R、IFNGR2则显著降低。结论儿童MG患者胸腺细胞异常增生与IL-1R、IL-6、IFNGR2、CCL25、CCR9等细胞因子及其受体的异常表达及信号分子BCL2的异常表达有关。

Objective To study the mechanism of thymic hyperplasia in children with myasthenia gravis（MG）.Methods The thymus tissues of MG patients with simple thymic hyperplasia were harvested,prepared and subjected to HE staining and immunohistochemical staining.The structure and molecular expression features of the thymus tissues were observed.The expressions of related cytokines,membrane molecules and the signal transduction molecules were measured by total RNA extraction and gene microarray analysis.Results The hyperplasia of thymocytes was obvious in MG patients.The expression of CD3 was strongly positive,and HLA-DR was predominantly expressed in the thymic medulla.A number of cytokines,membrane molecules and signal transduction molecules were found abnormally expressed in MG thymus tissues.The expressions of BCL2,CCL22,CCL25,CCL3,CCR7and CCR9 were dramatically increased in MG thymus,while those of CCL2,CSF3,CSF3R,CX3CL1,CXCL9,IL-1Rand IFNGR2were significantly reduced.Conclusion The thymic hyperplasia in MG children is associated with abnormal expressions of some cytokines（IL-1R,IL-6,IFNGR2,CCL25and CCR9）and signal transduction molecules（BCL2）.