EXPRESSION OF NEUROFILAMENTS AND OF A TITIN EPITOPE IN THYMIC EPITHELIAL TUMORS - IMPLICATIONS FOR THE PATHOGENESIS OF MYASTHENIA-GRAVIS

Autoantibodies against both striated muscle proteins, particularly tit in, and the acetylcholine receptor are a hallmark of thymoma-associate d myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable is these tumors. This stud y reports that in thymomas with cortical differentiation many of the n eoplastic epithelial cells expressed low and medium molecular weight n eurofilaments detected with several antibodies (on sections and blots) and at the RNA level (by reverse transcriptase polymerase chain react ion). Moreover, higher molecular weight forms sharing at least one epi tope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, is medullary and mixed thymomas, and especially in the normal thymus, immunoreacti vity with anti-neurofilament antibodies was rare. This aberrant overex pression of a titin epitope by epithelial cells with antigen-presentin g phenotype in an inappropriate cortical microenvironment suggests tha t they might autosensitize maturing T cells there and so initiate anti -titin autoimmunity in these patients.