重症肌无力患者胸腺瘤内Titin、Ryanodine受体表位表达

Titin and Ryanodine receptor epitopes are expressed in thymoma with myasthenia gravis patients

目的研究重症肌无力(MG)患者血清连接素抗体(Titin-ab)和 Ryanodine 受体抗体(RyR-ab)的水平,并探讨胸腺瘤内 Titin、RyR 表位的表达。方法应用 ELISA 法检测62例 MG 患者血清中 Titin-ab、RyR-ab 水平,以45例非 MG 的其他神经系统疾病患者和50名健康志愿者为对照组,采用免疫组织化学技术,对19例合并胸腺异常者[9例 MG 合并胸腺瘤(MGT)、6例 MG 合并胸腺增生(MGH)、2例 MG 合并胸腺萎缩(MGA)以及2例非 MG 胸腺癌(NMGTC)]的冰冻胸腺组织进行Titin、RyR 染色。结果 ELISA 法显示,MG 患者 Titin-ab 总阳性率为35.5%(22/62),其中以 MGT 组阳性率最高(82.3%,14/17);而 RyR-ab 阳性率为24.2%(15/62),也以 MGT 组阳性率最高(76.5%,13/17)。9例 MGT 的肿瘤上皮细胞中有7例存在 Titin 表位的膜表达和胞质内表达,有6例存在 RyR表位的膜表达;而 MGH 组、MGA 组、NMGTC 组和对照组均无阳性表达。结论 Titin-ab 和 RyR-ab 主要见于 MGT 患者。MGT 肿瘤上皮细胞存在 Titin、RyR 表位的表达。MGT 患者体内 Titin-ab 和 RyR-ab 很可能是胸腺瘤内微环境的改变激活 Titin、RyR 特异性 T 细胞,致敏 Titin、RyR 表位使其发生自身免疫反应的结果。

Objective To study the significance of Titin-ab and Ryanodine receptor-ab （RyR-ab） in the myasthenia gravis （MG） patients and the expression of Titin and RyR epitopes in thymoma of myasthenia gravis. Methods Using ELISA methods, the titer of the Titin-ab, RyR-ab in the sera of 62 patients with MG, as well as 45 cases non-MG with other neurologic disorders and 50 case of normal controls were determined,and Titin and RyR were studied with immunohistochemistry stain in the 19 samples of thymic tissues from 9 cases of MG with thymoma （ MGT）, 6 cases of MG with thymic hyperplasia （MGH） , 2 cases of MG with thymic atrophy （MGA）, and 2 cases of non-MG with thymic carcinoma （NMGTC）. Results The positive rate of Titin-ab in MG was 35.5% （22/62）, with the highest being 82.3% （14/17） in MGT group. The positive rate of RyR-ab was 24. 2% （ 15/62）, the highest being 76. 5% （13/17） in MGT group. Titin receptor epitopes were expressed in the transmembrane and cytoplasm region of thymoma epithelial cells of 7 cases of MGT patients, and RyR epitopes in the transmembrane region of thymoma epithelial cells of 6 cases of MGT; but no Titin nor RyR epitopes was identified in controls and such thymic pathological patterns, as MGH, MGA, NMGTC. Conclusions Titin-ab and RyR-ab are mostly found in MGT patients ; Titin and RyR epitopes are expressed in neoplasm epithelial cells of thymoma with myasthenia gravis ; it＇ s a result of autoimmunization of Titin and RyR epitopes irritated by Titin and RyR specific T cells activated by the change of pathogenic microenvionment inside the thymoma.