{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:24:31Z","timestamp":1791465871633,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T00:00:00Z","timestamp":1172793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra\u2010tumourous thymopoiesis and export of inefficiently tolerized T\u2010cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self\u2010antigens in the thymic medulla and plays an essential role in \u2018central\u2019 tolerance in both humans and mice. However, while inactivating <jats:italic>AIRE<\/jats:italic> mutations result in the \u2018autoimmune polyendocrinopathy syndrome type 1\u2019 (APS\u20101), its major features are not well reproduced in <jats:italic>AIRE<\/jats:italic>\u2010knock\u2010out mice. Therefore, alternative human disease scenarios with concomitant AIRE deficiency may be valuable tools to test conclusions drawn from mouse models. Here we show, in a large series, that \u223c95% of thymoma patients are \u2018chimeric\u2019; expression of AIRE and major AIRE\u2010related autoantigens (eg insulin) were undetectable in their tumours but maintained in their remnant thymic tissue and lymph nodes. Notably, despite the AIRE\u2010deficient thymopoiesis in thymomas, disorders and autoantibodies typical of APS\u20101 were distinctly uncommon in these patients. The one striking similarity was in the recently observed neutralizing anti\u2010type I interferon (IFN) antibodies, which are found at diagnosis in 100% of patients with APS\u20101 and in \u223c60% of patients with thymomas, as we show here. We conclude that APS\u20101 type autoantigens must be protected from autoimmunity by mechanisms that do not extend to the muscle autoantigens so frequently targeted in thymoma patients but so rarely recognized in APS\u20101. Thus our findings argue strongly for a tolerogenic function of AIRE beyond its role in negative T\u2010cell selection in human thymopoiesis, and\/or for specific autoimmunization against muscle in thymomas. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2141","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T12:04:04Z","timestamp":1172837044000},"page":"563-571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 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