Marx A, Wilisch A, Schultz A, Greiner A, Magi B, Pallini V, Schalke B, Toyka K, Nix W, Kirchner T, Müller-Hermelink H K
Institute of Pathology, University of Würzburg, Germany.
Am J Pathol. 1996 Jun;148(6):1839-50.
Autoantibodies against both striated muscle proteins, particularly titin, and the acetylcholine receptor are a hallmark of thymoma-associated myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable in these tumors. This study reports that in thymomas with cortical differentiation many of the neoplastic epithelial cells expressed low and medium molecular weight neurofilaments detected with several antibodies (on selections and blots) and at the RNA level (by reverse transcriptase polymerase chain reaction). Moreover, higher molecular weight forms sharing at least one epitope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, in medullary and mixed thymomas, and especially in the normal thymus, immunoreactivity with anti-neurofilament antibodies was rare. This aberrant overexpression of a titin epitope by epithelial cells with antigen-presenting phenotype in an inappropriate cortical microenvironment suggests that they might autosensitize maturing T cells there and so initiate anti-titin autoimmunity in these patients.
针对横纹肌蛋白（尤其是肌联蛋白）和乙酰胆碱受体的自身抗体是胸腺瘤相关重症肌无力的一个标志。然而，这些反应的刺激因素仍然不明，因为在这些肿瘤中无法检测到完整的肌联蛋白。本研究报告称，在具有皮质分化的胸腺瘤中，许多肿瘤上皮细胞表达了低分子量和中分子量神经丝，通过几种抗体（在切片和印迹上）以及RNA水平（通过逆转录聚合酶链反应）均可检测到。此外，与肌联蛋白共享至少一个表位的高分子量形式的检测频率略低，磷酸化程度更高的表位也是如此。与之形成鲜明对比的是，在髓质型和混合型胸腺瘤中，尤其是在正常胸腺中，抗神经丝抗体的免疫反应性很少见。在不适当的皮质微环境中，具有抗原呈递表型的上皮细胞异常过度表达肌联蛋白表位，这表明它们可能使那里成熟的T细胞自身致敏，从而在这些患者中引发抗肌联蛋白自身免疫。
