{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:46:00Z","timestamp":1788965160191,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>Generation of autoreactive CD4<jats:sup>+<\/jats:sup> effector T cells and defective production of regulatory CD4<jats:sup>+<\/jats:sup> T cells inside thymomas contribute to the development of myasthenia gravis (MG) in &gt;90% of MG(+) thymomas. The molecular basis of these abnormalities is unknown. We report here that a) expression levels of class II major histocompatibility complex (MHCII) genes are variably decreased in thymomas, most prominently in histological WHO types A and AB; b) epithelial cells of type A and AB thymomas exhibit signal transducer and activator of transcription (STAT\u20101)\u2010related defects of interferon\u2010\u03b3 (IFN\u2010\u03b3) signaling and human leukocyte antigen (HLA)\u2010DR expression <jats:italic>in vitro<\/jats:italic>; c) the promoter III (pIII)\u2010 and pIV\u2010driven splice variants of the MHCII transactivator (CIITA) play a key role in MHCII gene expression in thymus and thymomas; and d) the pIV CIITA promoter is heavily methylated in thymomas. Recently, we also found that expression of the autoimmune regulator (AIRE) gene is absent from \u223c95% of thymomas. Among all theses abnormalities, only <jats:italic>better preserved<\/jats:italic> expression levels of MHCII (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001) in thymomas were significantly associated with the presence of MG. Taking the association of a gain\u2010of\u2010function polymorphism of the CTLA\u20104 and PTPN22 gene with MG in thymomas into account, we conclude that these <jats:italic>acquired cellular<\/jats:italic> abnormalities of the thymoma microenvironment in concert with <jats:italic>inherited genetic<\/jats:italic> high\u2010risk polymorphisms of immunoregulatory genes have an impact on intratumorous thymopoiesis and appear to tip the balance toward central tolerance failure and development of MG. The findings imply that IFN\u2010\u03b3 and STAT\u20101 signaling play a role in MHCII expression in the human thymus and in the pathogenesis of paraneoplastic MG.<\/jats:p>","DOI":"10.1196\/annals.1405.018","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T23:23:28Z","timestamp":1214004208000},"page":"143-156","source":"Crossref","is-referenced-by-count":51,"title":["<i>Common Cellular and Diverse Genetic Basis of Thymoma\u2010associated Myasthenia Gravis<\/i>"],"prefix":"10.1111","volume":"1132","author":[{"given":"Philipp","family":"Str\u00f6bel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Yu","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei","family":"Chuvpilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zettl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiemo","family":"Katzenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Kalbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rieckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Nix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"Schalke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Konrad","family":"M\u00fcller\u2010Hermelink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4rt","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Marx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"e_1_2_7_2_2","first-page":"145","volume-title":"World Health Organization Classification of Tumours. 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