Titin Epitope in Thymoma
Autoantibodies against striated muscle proteins (particularly against titin), neuronal structures and the acetylcholine receptor are a hallmark of paraneoplastic Myasthenia gravis (MG). The stimulus for this autoimmunity remains enigmatic, because complete titin or nicotinic acetylcholine receptors are not found in these tumors. This study reports, that a monoclonal antibody (mAb 155) directed against the “Very Immunogenic Cytoplasmic Region” (VICE-α) of the acetylcholine receptor (α373 – 380) crossreacts with a 153 kD molecule only in cortical type thymomas. We could show by immunostaining and west-ernblotting that this molecule might be the medium molecular weight neurofilament NF-M. Since NF-M and titin share a common epitope, we observed that a crossreactive anti-titin antibody showed a similar staining pattern in cortical type thymomas as antibodies against NF-M and mAb 155. We suggest that one molecule, NF-M, which does contain titin and AChR epitopes and which is expressed in an inappropriate cortical environment in thymoma, might autosensitize maturing T-cells and initiate autoimmunity in patients with paraneoplastic MG against the three main autoantigen targets: AChR, titin and neuronal structures.
KeywordsAcetylcholine Receptor Thymic Carcinoma Striate Muscle Protein Myoid Cell Thymic Epithelial Tumor
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