摘要
目的探讨胸腺瘤患者发生重症肌无力(myasthenia gravis,MG)的机制及Fas基因在MG发病中的作用。方法收集131例胸腺瘤患者,按是否合并MG分为合并MG组(70例)和不合并MG组(61例)两组。应用免疫组织化学、蛋白电泳、聚合酶链反应和酶联免疫吸附等方法检测两组患者胸腺淋巴细胞Fas蛋白表达和血清可溶性Fas(sFas)水平,应用DNA测序技术检测Fas基因结构变异。结果胸腺瘤合并MG组患者胸腺淋巴细胞Fas表达水平明显低于胸腺瘤不合并MG组,sFas含量〔(3879.06±706.51)pg/mL〕明显高于胸腺瘤不合并MG组〔(1868.18±391.46)pg/mL〕(P<0.01);胸腺瘤合并MG组胸腺淋巴细胞Fas基因第6外显子16和21位点T→G置换突变发生率分别为65%和75%,明显高于胸腺瘤不合并MG组(两位点均为5%)(P<0.05)。结论胸腺淋巴细胞Fas基因外显子6某些位点发生突变,所编码的Fas蛋白跨膜区变异或缺乏跨膜区而导致Fas结构和功能的改变可能是MG发生的主要原因。
Objective To investigate the cause of myasthenia gravis （MG） in patients with thymoma and how Fas gene effects the pathogenesis of MG. Methods The study included 131 patients with tbymoma who were divided into two groups according to whether they had MG （Group A） or not （Group B）. The expression of Fas protein in thymocytes and serum soluble Fas （sFas） were measured by immunohistochemistry, Western Blot, reverse transcriptase polymerase chain reaction （RT-PCR） and enzyme linked immunosorbent assay （ELISA）, and the Fas gene mutations were detected by DNA sequencing technique. Results The Fas expression of thymic lymphocyte in Group A was obviously lower than that in Group B; however, the mean value of sFas in Group A was much higher than that in Group B [ （3879.06±706.51） pg/mL vs （1868. 18±391.46） pg/mL], with a significant difference （P〈0.01）. The gene sequencing indicated that the incidences of replacement mutation （T→ G） were 65% and 75% at site 16 and 21, exon 6, in patients with MG, which was obviously higher than that in patients without MG （ both 5%）, showing a notable statistical difference （P〈0.05）. Conclusions In thymoma patients with MG, mutations may happen in Fas exon 6 in thymic lymphocyte, the transmembrane domain of the coded Fas protein was changed or lost, which resulted in the change of structure and function of Fas, and that may be one of the main pathogenesis of MG.
出处
《中国神经免疫学和神经病学杂志》
CAS
北大核心
2013年第2期116-120,共5页
Chinese Journal of Neuroimmunology and Neurology
基金
辽宁省自然科学基金资助项目(20042088)
