Wilisch A, Gutsche S, Hoffacker V, Schultz A, Tzartos S, Nix W, Schalke B, Schneider C, Müller-Hermelink H K, Marx A
Institute of Pathology, University of Würzburg, Germany.
Neurology. 1999 Apr 22;52(7):1460-6. doi: 10.1212/wnl.52.7.1460.
To investigate the association of MG with the transcription of muscular or neuronal acetylcholine receptor (AChR) subunit genes in thymomas.
Many steps in the pathogenesis of MG have been elucidated but, with rare exceptions, its etiology is unknown. In patients with MG with thymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmatic why MG develops in some patients but not in others.
Reverse transcriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies were carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between thymoma subtypes.
Considering all thymomas (n = 35), no correlation was found between MG status and AChR gene expression as detected by RT-PCR. However, when histologically defined thymoma subtypes were studied separately, transcription of the muscular AChR P3A- alpha-subunit gene was significantly associated (alpha < 0.01) with the occurrence of MG in mixed thymomas (n = 17), but not in thymomas of the cortical type. For the other muscular AChR subunits (P3A+ alpha isoform, beta, gamma, delta, and epsilon) and the alpha2 and beta4 neuronal AChR subunits, no such correlation was detected.
Expression of the P3A AChR alpha-subunit gene might be important for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically different thymoma subtypes.
研究重症肌无力（MG）与胸腺瘤中肌肉型或神经元型乙酰胆碱受体（AChR）亚基基因转录之间的关联。
MG发病机制中的许多步骤已被阐明，但除极少数例外，其病因尚不清楚。在合并胸腺瘤的MG患者中，肿瘤可能引发针对AChR的自身免疫，但为何MG在部分患者中发生而在其他患者中不发生仍不清楚。
采用逆转录酶（RT）-PCR、免疫组织化学和免疫荧光研究，对35例胸腺瘤患者的AChR表达进行检测。采用统计学分析确定胸腺瘤亚型之间的显著差异。
就所有胸腺瘤（n = 35）而言，RT-PCR检测的MG状态与AChR基因表达之间未发现相关性。然而，当分别研究组织学定义的胸腺瘤亚型时，肌肉型AChR P3A-α亚基基因的转录与混合型胸腺瘤（n = 17）中MG的发生显著相关（α < 0.01），但在皮质型胸腺瘤中无此相关性。对于其他肌肉型AChR亚基（P3A + α异构体、β、γ、δ和ε）以及α2和β4神经元型AChR亚基，未检测到此类相关性。
P3A AChR α亚基基因的表达可能对混合型胸腺瘤中MG的发病机制很重要，提示组织学不同胸腺瘤亚型患者的副肿瘤性MG存在病因异质性。
