Chuang Wen-Yu, Ströbel Philipp, Gold Ralf, Nix Wilfred, Schalke Berthold, Kiefer Reinhard, Opitz Andreas, Klinker Erdwine, Müller-Hermelink Hans K, Marx Alexander
Institute of Pathology, University of Würzburg, Würzburg, Germany.
Ann Neurol. 2005 Oct;58(4):644-8. doi: 10.1002/ana.20577.
Myasthenia gravis (MG) in thymoma patients depends critically on intratumorous generation and export of mature autoreactive CD4+ T cells. Why non-MG thymomas fail to produce CD4+ T cells is unknown. We studied three single-nucleotide polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4(CTLA4) gene in thymoma patients, nonthymoma early-onset MG patients, and control subjects. Surprisingly, the CTLA4high genotype +49A/A, which is protective against several autoimmune diseases, exerted a prominent predisposing effect to paraneoplastic MG in thymoma patients. The unusual disease association with a CTLA4high genotype implies a unique pathogenesis of paraneoplastic MG, with high CTLA4 levels possibly supporting the nontolerogenic selection of CD4+ T cells in MG-associated thymomas.
胸腺瘤患者的重症肌无力（MG）严重依赖肿瘤内成熟自身反应性CD4+ T细胞的产生和输出。非MG胸腺瘤无法产生CD4+ T细胞的原因尚不清楚。我们研究了胸腺瘤患者、非胸腺瘤早发型MG患者和对照受试者中细胞毒性T淋巴细胞相关抗原4（CTLA4）基因的三个单核苷酸多态性。令人惊讶的是，对几种自身免疫性疾病具有保护作用的CTLA4高基因型+49A/A，对胸腺瘤患者的副肿瘤性MG具有显著的易患作用。与CTLA4高基因型的异常疾病关联意味着副肿瘤性MG具有独特的发病机制，高CTLA4水平可能支持MG相关胸腺瘤中CD4+ T细胞的非耐受性选择。
