{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T09:00:52Z","timestamp":1789722052065,"version":"4.0.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anti-PIT-1 antibody syndrome has recently been reported and characterized by acquired growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies associated with autoimmunity to a pituitary specific transcription factor PIT-1, which plays an essential role in GH-, PRL-, and TSH-producing cells. Although circulating anti-PIT-1 antibody and PIT-1-reactive cytotoxic T cells (CTLs) were detected in the patients, the pathophysiology and precise mechanisms for the autoimmunity remain unclarified. During the follow up, thymoma was diagnosed in all 3 cases with anti-PIT-1 antibody syndrome. Immunohistochemical analysis revealed that PIT-1 was strongly expressed in neoplastic cortical thymic epithelial cells. Importantly, after thymectomy, the titer of anti-PIT-1 antibody decreased and reactivity of CTLs toward PIT-1 diminished. These data strongly suggest that the aberrant expression of PIT-1 in the thymoma plays a causal role in the development of this syndrome. Thus, we define that this syndrome is a novel thymoma-associated autoimmune disease.<\/jats:p>","DOI":"10.1038\/srep43060","type":"journal-article","created":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T10:19:42Z","timestamp":1487585982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A novel thymoma-associated autoimmune disease: Anti-PIT-1 antibody syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"Hironori","family":"Bando","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genzo","family":"Iguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Okimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Odake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusaku","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Suda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Nishizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Fukuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Mokubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Tojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimasa","family":"Maniwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"key":"BFsrep43060_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.beem.2010.10.014","volume":"25","author":"R Pf\u00e4ffle","year":"2011","unstructured":"Pf\u00e4ffle, R. & Klammt, J. Pituitary transcription factors in the aetiology of combined pituitary hormone deficiency. Best Pract Res Clin Endocrinol Metab. 25, 43\u201360 (2011).","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"BFsrep43060_CR2","doi-asserted-by":"crossref","unstructured":"Higham, C. E., Johannsson, G. & Shalet, S. M. Hypopituitarism. Lancet. [Epub ahead of print] (2016).","DOI":"10.1016\/S0140-6736(16)30053-8"},{"key":"BFsrep43060_CR3","doi-asserted-by":"crossref","unstructured":"Fleseriu, M. et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. [Epub ahead of print] (2016).","DOI":"10.1210\/jc.2016-2118"},{"key":"BFsrep43060_CR4","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/S0140-6736(07)60673-4","volume":"369","author":"HJ Schneider","year":"2007","unstructured":"Schneider, H. J., Aimaretti, G., Kreitschmann-Andermahr, I., Stalla, G. K. & Ghigo, E. Hypopituitarism. Lancet. 369, 1461\u20131470 (2007).","journal-title":"Lancet."},{"key":"BFsrep43060_CR5","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1210\/er.2004-0011","volume":"26","author":"P Caturegli","year":"2005","unstructured":"Caturegli, P. et al. Autoimmune hypophysitis. Endocr Rev. 26, 599\u2013614 (2005).","journal-title":"Endocr Rev."},{"key":"BFsrep43060_CR6","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1507\/endocrj.EJ14-0369","volume":"62","author":"A Kiyota","year":"2015","unstructured":"Kiyota, A. et al. Identification of the novel autoantigen candidate Rab GDP dissociation inhibitor alpha in isolated adrenocorticotropin deficiency. Endocr J. 62, 153\u2013160 (2015).","journal-title":"Endocr J."},{"key":"BFsrep43060_CR7","first-page":"288","volume":"55","author":"T Takao","year":"2001","unstructured":"Takao, T. et al. Antipituitary antibodies in patients with lymphocytic hypophysitis. Horm Res. 55, 288\u2013292 (2001).","journal-title":"Horm Res."},{"key":"BFsrep43060_CR8","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.ceb.2007.09.011","volume":"19","author":"X Zhu","year":"2007","unstructured":"Zhu, X., Wang, J., Ju, B. G. & Rosenfeld, M. G. Signaling and epigenetic regulation of pituitary development. Curr Opin Cell Biol. 19, 605\u2013611 (2007).","journal-title":"Curr Opin Cell Biol"},{"key":"BFsrep43060_CR9","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/ng0492-56","volume":"1","author":"K Tatsumi","year":"1992","unstructured":"Tatsumi, K. et al. Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Nat. Genet. 1, 56\u201358 (1992).","journal-title":"Nat. Genet"},{"key":"BFsrep43060_CR10","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1172\/JCI44073","volume":"121","author":"M Yamamoto","year":"2011","unstructured":"Yamamoto, M. et al. Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans. J Clin Invest. 121, 113\u2013119 (2011).","journal-title":"J Clin Invest"},{"key":"BFsrep43060_CR11","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nrendo.2011.53","volume":"7","author":"J Drouin","year":"2011","unstructured":"Drouin, J. & Takayasu, S. Autoimmunity: acquired versus inherited pituitary deficiency - same difference? Nat Rev Endocrinol. 7, 255\u2013256 (2011).","journal-title":"Nat Rev Endocrinol"},{"key":"BFsrep43060_CR12","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/nrendo.2010.40","volume":"6","author":"AW Michels","year":"2010","unstructured":"Michels, A. W. & Gottlieb, P. A. Autoimmune polyglandular syndromes. Nat Rev Endocrinol. 6, 270\u2013277 (2010).","journal-title":"Nat Rev Endocrinol"},{"key":"BFsrep43060_CR13","doi-asserted-by":"publisher","first-page":"E1744","DOI":"10.1210\/jc.2014-1769","volume":"99","author":"H Bando","year":"2014","unstructured":"Bando, H. et al. Involvement of PIT-1-reactive cytotoxic T lymphocytes in anti-PIT-1 antibody syndrome. J Clin Endocrinol Metab. 99, E1744\u2013E1749 (2014).","journal-title":"J Clin Endocrinol Metab"},{"key":"BFsrep43060_CR14","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3389\/fimmu.2014.00411","volume":"5","author":"JF Miller","year":"2014","unstructured":"Miller, J. F. Revisiting thymus function. Front Immunol. 5, 411 (2014).","journal-title":"Front Immunol"},{"key":"BFsrep43060_CR15","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nri3667","volume":"14","author":"L Klein","year":"2014","unstructured":"Klein, L., Kyewski, B., Allen, P. M. & Hogquist, K. A. Positive and negative selection of the T cell repertoire: what thymocytes see (and don\u2019t see). Nat Rev Immunol. 14, 377\u2013391 (2014).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep43060_CR16","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.4049\/jimmunol.157.8.3752","volume":"157","author":"A Wakkach","year":"1996","unstructured":"Wakkach, A. et al. Expression of acetylcholine receptor genes in human thymic epithelial cells: implications for myasthenia gravis. J Immunol. 157, 3752\u20133760 (1996).","journal-title":"J Immunol."},{"key":"BFsrep43060_CR17","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3109\/08916930903555935","volume":"43","author":"A Marx","year":"2010","unstructured":"Marx, A. et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity. 43, 413\u2013427 (2010).","journal-title":"Autoimmunity"},{"key":"BFsrep43060_CR18","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s00595-012-0318-2","volume":"43","author":"Y Fujii","year":"2013","unstructured":"Fujii, Y. Thymus, thymoma and myasthenia gravis. Surg Today 43, 461\u2013466 (2013).","journal-title":"Surg Today"},{"key":"BFsrep43060_CR19","first-page":"290","volume":"12","author":"H Bando","year":"2015","unstructured":"Bando, H., Iguchi, G., Yamamoto, M., Hidaka-Takeno, R. & Takahashi, Y. Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism. Pediatr Endocrinol Rev. 12, 290\u2013296 (2015).","journal-title":"Pediatr Endocrinol Rev"},{"key":"BFsrep43060_CR20","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jneuroim.2008.06.016","volume":"201\u2013202","author":"CA MacLennan","year":"2008","unstructured":"MacLennan, C. A. et al. Preferential expression of AChR epsilon-subunit in thymomas from patients with myasthenia gravis. J Neuroimmunol. 201\u2013202, 28\u201332 (2008).","journal-title":"J Neuroimmunol."},{"key":"BFsrep43060_CR21","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.1016\/j.athoracsur.2005.11.067","volume":"81","author":"FC Detterbeck","year":"2006","unstructured":"Detterbeck, F. C. Clinical value of the WHO classification system of thymoma. Ann Thorac Surg. 81, 2328\u20132334 (2006).","journal-title":"Ann Thorac Surg"},{"key":"BFsrep43060_CR22","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.autrev.2015.09.005","volume":"15","author":"C Bernard","year":"2016","unstructured":"Bernard, C. et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev. 15, 82\u201392 (2016).","journal-title":"Autoimmun Rev."},{"key":"BFsrep43060_CR23","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.bbadis.2014.11.022","volume":"1852","author":"JC Ha","year":"2015","unstructured":"Ha, J. C. & Richman, D. P. Myasthenia gravis and related disorders: Pathology and molecular pathogenesis. Biochim Biophys Acta. 1852, 651\u2013657 (2015).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep43060_CR24","doi-asserted-by":"publisher","first-page":"7336","DOI":"10.1038\/srep07336","volume":"4","author":"Y Wang","year":"2014","unstructured":"Wang, Y. et al. Mutations of epigenetic regulatory genes are common in thymic carcinomas. Sci Rep. 4, 7336 (2014).","journal-title":"Sci Rep"},{"key":"BFsrep43060_CR25","doi-asserted-by":"publisher","first-page":"4289","DOI":"10.1172\/JCI42015","volume":"120","author":"I Ben-Batalla","year":"2010","unstructured":"Ben-Batalla, I. et al. Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis. J Clin Invest. 120, 4289\u20134302 (2010).","journal-title":"J Clin Invest"},{"key":"BFsrep43060_CR26","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1006\/excr.1998.4232","volume":"245","author":"JA Costoya","year":"1998","unstructured":"Costoya, J. A. et al. Correlation of Pit-1 gene expression and Pit-1 content with proliferation and differentiation in human myeloid leukemic cells. Exp Cell Res. 245, 132\u2013136 (1998).","journal-title":"Exp Cell Res"},{"key":"BFsrep43060_CR27","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/nrc907","volume":"2","author":"C Abate-Shen","year":"2002","unstructured":"Abate-Shen, C. Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer. 2, 777\u2013785 (2002).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep43060_CR28","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/(SICI)1097-0215(19990331)81:1<104::AID-IJC18>3.0.CO;2-Q","volume":"81","author":"T Jin","year":"1999","unstructured":"Jin, T. et al. Examination of POU homeobox gene expression in human breast cancer cells. Int J Cancer. 81, 104\u2013112 (1999).","journal-title":"Int J Cancer"},{"key":"BFsrep43060_CR29","doi-asserted-by":"publisher","first-page":"6684","DOI":"10.1038\/sj.onc.1203072","volume":"18","author":"V Budhram-Mahadeo","year":"1999","unstructured":"Budhram-Mahadeo, V., Ndisang, D., Ward, T., Weber, B. L. & Latchman, D. S. The Brn-3b POU family transcription factor represses expression of the BRCA-1 anti-oncogene in breast cancer cells. Oncogene. 18, 6684\u20136691 (1999).","journal-title":"Oncogene"},{"key":"BFsrep43060_CR30","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1056\/NEJM198209233071301","volume":"307","author":"DB Drachman","year":"1982","unstructured":"Drachman, D. B., Adams, R. N., Josifek, L. F. & Self, S. G. Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis. N Engl J Med. 307, 769\u2013775 (1982).","journal-title":"N Engl J Med"},{"key":"BFsrep43060_CR31","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1212\/WNL.43.6.1167","volume":"43","author":"S Nakano","year":"1993","unstructured":"Nakano, S. & Engel, A. G. Myasthenia gravis: quantitative immunocytochemical analysis of inflammatory cells and detection of complement membrane attack complex at the end-plate in 30 patients. Neurology. 43, 1167\u20131172 (1993).","journal-title":"Neurology"},{"key":"BFsrep43060_CR32","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s10875-007-9147-2","volume":"28","author":"A Fattorossi","year":"2008","unstructured":"Fattorossi, A. et al. Thymopoiesis, regulatory T cells, and TCRVbeta expression in thymoma with and without myasthenia gravis, and modulatory effects of steroid therapy. J Clin Immunol. 28, 194\u2013206 (2008).","journal-title":"J Clin Immunol"},{"key":"BFsrep43060_CR33","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1212\/WNL.30.5.557","volume":"30","author":"RS Tindall","year":"1980","unstructured":"Tindall, R. S. Humoral immunity in myasthenia gravis: effect of steroids and thymectomy. Neurology. 30, 554\u2013557 (1980)","journal-title":"Neurology"},{"key":"BFsrep43060_CR34","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1055\/s-2004-829596","volume":"24","author":"A Jaretzki","year":"2004","unstructured":"Jaretzki, A., Steinglass, K. M. & Sonett, J. R. Thymectomy in the management of myasthenia gravis. Semin Neurol. 24, 49\u201362 (2004).","journal-title":"Semin Neurol."},{"key":"BFsrep43060_CR35","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3109\/08916930903555935","volume":"43","author":"A Marx","year":"2010","unstructured":"Marx, A. et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity. 43, 413\u2013427 (2010).","journal-title":"Autoimmunity"},{"key":"BFsrep43060_CR36","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1056\/NEJMra023009","volume":"349","author":"RB Darnell","year":"2003","unstructured":"Darnell, R. B. & Posner, J. B. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 349, 1543\u20131554 (2003).","journal-title":"N Engl J Med"},{"key":"BFsrep43060_CR37","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S1474-4422(02)00135-7","volume":"1","author":"R Voltz","year":"2002","unstructured":"Voltz, R. Paraneoplastic neurological syndromes: an update on diagnosis, pathogenesis, and therapy. Lancet Neurol. 1, 294\u2013305 (2002).","journal-title":"Lancet Neurol."},{"key":"BFsrep43060_CR38","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0065-2423(07)44005-7","volume":"44","author":"A Storstein","year":"2007","unstructured":"Storstein, A. & Vedeler, C. A. Paraneoplastic neurological syndromes and onconeural antibodies: clinical and immunological aspects. Adv Clin Chem. 44, 143\u2013185 (2007).","journal-title":"Adv Clin Chem"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep43060","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep43060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep43060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:38:09Z","timestamp":1692693489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep43060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,20]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,24]]}},"alternative-id":["BFsrep43060"],"URL":"https:\/\/doi.org\/10.1038\/srep43060","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,20]]},"assertion":[{"value":"11 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43060"}}