{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:29:50Z","timestamp":1790753390782,"version":"4.1.0"},"reference-count":42,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture","award":["17K16165"],"award-info":[{"award-number":["17K16165"]}]},{"name":"Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture","award":["23591354"],"award-info":[{"award-number":["23591354"]}]},{"name":"Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture","award":["15K094315"],"award-info":[{"award-number":["15K094315"]}]},{"name":"Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture","award":["18K08514"],"award-info":[{"award-number":["18K08514"]}]},{"name":"Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture","award":["23659477"],"award-info":[{"award-number":["23659477"]}]},{"name":"Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture","award":["26670459"],"award-info":[{"award-number":["26670459"]}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17bm0804012h0001"],"award-info":[{"award-number":["17bm0804012h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Anti\u2013pituitary-specific transcriptional factor-1 (anti\u2013PIT-1) antibody syndrome is characterized by acquired and specific deficiencies in growth hormone, prolactin, and thyroid-stimulating hormone. Although PIT-1\u2013reactive cytotoxic T lymphocytes (CTLs) have been speculated to recognize anterior pituitary cells and to cause the injury in the pathogenesis of the syndrome, it remains unclear whether endogenous PIT-1 protein is processed through the proteolytic pathway and presented as an antigen on anterior pituitary cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To examine how PIT-1 protein is processed and whether its epitope is presented by major histocompatibility complex (MHC)\/HLA class I on anterior pituitary cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Immunofluorescence staining and proximity ligation assay (PLA) were performed using anti\u2013PIT-1 antibody and patients\u2019 sera on PIT-1\u2013expressing cell line GH3 cells and human induced pluripotent stem cell (iPSC)-derived pituitary tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PIT-1 was colocalized with MHC class I molecules, calnexin, and GM130 in the cytosol. PLA results showed that PIT-1 epitope was presented by MHC\/HLA class I molecules on the cell surface of GH3 cells and iPSC-derived pituitary cells. The number of PIT-1\/HLA complexes on the cell surface of pituitary cells in the patient was comparable with that in the control subject.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data indicate that PIT-1 protein is processed in the antigen presentation pathway and that its epitopes are presented by in MHC\/HLA class I on anterior pituitary cells, supporting the hypothesis that PIT-1\u2013reactive CTLs caused the cell-specific damage. It is also suggested that number of epitope presentation was not associated with the pathogenesis of anti\u2013PIT-1 antibody syndrome.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/js.2019-00243","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T09:04:32Z","timestamp":1566810272000},"page":"1969-1978","source":"Crossref","is-referenced-by-count":28,"title":["Pathogenesis of Anti\u2013PIT-1 Antibody Syndrome: PIT-1 Presentation by HLA Class I on Anterior Pituitary Cells"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-9857","authenticated-orcid":false,"given":"Keitaro","family":"Kanie","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Bando","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genzo","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"},{"name":"Medical Center for Student Health, Kobe University, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Muguruma","sequence":"additional","affiliation":[{"name":"Department of iPS Cell Applied Medicine, Kansai Medical University, Hirakata, Japan"},{"name":"RIKEN Center for Biosystems Dynamics Research, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusaku","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Hidaka-Takeno","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Okimura","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Suda","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-9246","authenticated-orcid":false,"given":"Yutaka","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"2019101009283956500_bib1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000452907","article-title":"A novel clinical entity of autoimmune endocrinopathy: anti-PIT-1 antibody syndrome","volume":"48","author":"Iguchi","year":"2017","journal-title":"Front Horm Res"},{"issue":"1","key":"2019101009283956500_bib2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1172\/JCI44073","article-title":"Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans","volume":"121","author":"Yamamoto","year":"2011","journal-title":"J Clin Invest"},{"issue":"1","key":"2019101009283956500_bib3","doi-asserted-by":"crossref","first-page":"43060","DOI":"10.1038\/srep43060","article-title":"A novel thymoma-associated autoimmune disease: anti-PIT-1 antibody syndrome","volume":"7","author":"Bando","year":"2017","journal-title":"Sci Rep"},{"issue":"9","key":"2019101009283956500_bib4","doi-asserted-by":"crossref","first-page":"E1744","DOI":"10.1210\/jc.2014-1769","article-title":"Involvement of PIT-1-reactive cytotoxic T lymphocytes in anti-PIT-1 antibody syndrome","volume":"99","author":"Bando","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2019101009283956500_bib5","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1097\/00007890-198409000-00018","article-title":"The detailed distribution of HLA-A, B, C antigens in normal human organs","volume":"38","author":"Daar","year":"1984","journal-title":"Transplantation"},{"issue":"20","key":"2019101009283956500_bib6","doi-asserted-by":"crossref","first-page":"eaao4013","DOI":"10.1126\/sciimmunol.aao4013","article-title":"Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors","volume":"3","author":"Culina","year":"2018","journal-title":"Sci Immunol"},{"key":"2019101009283956500_bib7","doi-asserted-by":"crossref","first-page":"348546","DOI":"10.1155\/2013\/348546","article-title":"Recent advances in the pathogenesis of autoimmune hair loss disease alopecia areata","volume":"2013","author":"Ito","year":"2013","journal-title":"Clin Dev Immunol"},{"issue":"1","key":"2019101009283956500_bib8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1152\/physrev.00025.2001","article-title":"The transporter associated with antigen processing: function and implications in human diseases","volume":"82","author":"Lankat-Buttgereit","year":"2002","journal-title":"Physiol Rev"},{"issue":"6779","key":"2019101009283956500_bib9","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/35008096","article-title":"Rapid degradation of a large fraction of newly synthesized proteins by proteasomes","volume":"404","author":"Schubert","year":"2000","journal-title":"Nature"},{"issue":"5","key":"2019101009283956500_bib10","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"issue":"33","key":"2019101009283956500_bib11","doi-asserted-by":"crossref","first-page":"11796","DOI":"10.1073\/pnas.0803078105","article-title":"Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation","volume":"105","author":"Wataya","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"2019101009283956500_bib12","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/stem.1293","article-title":"An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells","volume":"31","author":"Okita","year":"2013","journal-title":"Stem Cells"},{"issue":"6","key":"2019101009283956500_bib13","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/0092-8674(90)90385-R","article-title":"The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain","volume":"62","author":"McMahon","year":"1990","journal-title":"Cell"},{"issue":"1","key":"2019101009283956500_bib14","doi-asserted-by":"crossref","first-page":"10351","DOI":"10.1038\/ncomms10351","article-title":"Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells","volume":"7","author":"Ozone","year":"2016","journal-title":"Nat Commun"},{"key":"2019101009283956500_bib15","unstructured":"RRID:AB_2166884, https:\/\/scicrunch.org\/resolver\/AB_2166884."},{"key":"2019101009283956500_bib16","unstructured":"RRID:AB_476845, https:\/\/scicrunch.org\/resolver\/AB_476845."},{"key":"2019101009283956500_bib17","unstructured":"RRID:AB_532244, https:\/\/scicrunch.org\/resolver\/AB_532244."},{"key":"2019101009283956500_bib18","unstructured":"RRID:AB_322394, https:\/\/scicrunch.org\/resolver\/AB_322394."},{"key":"2019101009283956500_bib19","unstructured":"RRID:AB_1269092, https:\/\/scicrunch.org\/resolver\/AB_1269092."},{"key":"2019101009283956500_bib20","unstructured":"RRID:AB_10894731, https:\/\/scicrunch.org\/resolver\/AB_10894731."},{"key":"2019101009283956500_bib21","unstructured":"RRID:AB_10893722, https:\/\/scicrunch.org\/resolver\/AB_10893722."},{"key":"2019101009283956500_bib22","unstructured":"RRID:AB_2534012, https:\/\/scicrunch.org\/resolver\/AB_2534012."},{"key":"2019101009283956500_bib23","unstructured":"RRID:AB_2732856, https:\/\/scicrunch.org\/resolver\/AB_2732856."},{"key":"2019101009283956500_bib24","unstructured":"RRID:AB_2534016, https:\/\/scicrunch.org\/resolver\/AB_2534016."},{"key":"2019101009283956500_bib25","unstructured":"RRID:AB_2810940, https:\/\/scicrunch.org\/resolver\/AB_2810940."},{"key":"2019101009283956500_bib26","unstructured":"RRID:AB_2810942, https:\/\/scicrunch.org\/resolver\/AB_2810942."},{"key":"2019101009283956500_bib27","unstructured":"RRID:AB_2810939, https:\/\/scicrunch.org\/resolver\/AB_2810939."},{"key":"2019101009283956500_bib28","unstructured":"RRID:AB_2713942, https:\/\/scicrunch.org\/resolver\/AB_2713942."},{"key":"2019101009283956500_bib29","unstructured":"RRID:SCR_017202, https:\/\/scicrunch.org\/resolver\/SCR_017202."},{"key":"2019101009283956500_bib30","unstructured":"RRID:SCR_017377, https:\/\/scicrunch.org\/resolver\/SCR_017377."},{"key":"2019101009283956500_bib31","unstructured":"RRID:SCR_017375, https:\/\/scicrunch.org\/resolver\/SCR_17375."},{"key":"2019101009283956500_bib32","unstructured":"RRID:SCR_013672, https:\/\/scicrunch.org\/resolver\/SCR_013672."},{"issue":"3","key":"2019101009283956500_bib33","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1083\/jcb.43.3.432","article-title":"Control of growth hormone production by a clonal strain of rat pituitary cells: stimulation by hydrocortisone","volume":"43","author":"Bancroft","year":"1969","journal-title":"J Cell Biol"},{"issue":"10","key":"2019101009283956500_bib34","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1073\/pnas.1401105111","article-title":"Autoantibodies to IgG\/HLA class II complexes are associated with rheumatoid arthritis susceptibility","volume":"111","author":"Jin","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2019101009283956500_bib35","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.immunol.16.1.323","article-title":"Mechanisms of MHC class I--restricted antigen processing","volume":"16","author":"Pamer","year":"1998","journal-title":"Annu Rev Immunol"},{"issue":"3-4","key":"2019101009283956500_bib36","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.trim.2005.03.021","article-title":"HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms","volume":"14","author":"Thorsby","year":"2005","journal-title":"Transpl Immunol"},{"key":"2019101009283956500_bib37","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/bs.ircmb.2018.05.008","article-title":"T lymphocytes and autoimmunity","volume":"341","author":"Khan","year":"2018","journal-title":"Int Rev Cell Mol Biol"},{"issue":"9","key":"2019101009283956500_bib38","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1001\/archinte.1980.00330200119034","article-title":"Lymphoid hypophysitis with selective adrenocorticotropic hormone deficiency","volume":"140","author":"Richtsmeier","year":"1980","journal-title":"Arch Intern Med"},{"issue":"2","key":"2019101009283956500_bib39","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/00000433-199706000-00020","article-title":"Isolated adrenocorticotropic hormone deficiency: an autopsy case of adrenal crisis. A case report","volume":"18","author":"Kubo","year":"1997","journal-title":"Am J Forensic Med Pathol"},{"issue":"3","key":"2019101009283956500_bib40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1365-2265.2011.04056.x","article-title":"Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism","volume":"75","author":"De Bellis","year":"2011","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"2019101009283956500_bib41","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s11102-008-0164-9","article-title":"Isolated acquired ACTH deficiency and primary hypothyroidism: a short series and review","volume":"14","author":"Hannon","year":"2011","journal-title":"Pituitary"},{"issue":"4","key":"2019101009283956500_bib42","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2169\/internalmedicine.9074-17","article-title":"Isolated adrenocorticotropin deficiency due to nivolumab-induced hypophysitis in a patient with advanced lung adenocarcinoma: a case report and literature review","volume":"57","author":"Ohara","year":"2018","journal-title":"Intern Med"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/js.2019-00243\/29207012\/js.2019-00243.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/3\/11\/1969\/30128353\/js.2019-00243.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/3\/11\/1969\/30128353\/js.2019-00243.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T18:09:16Z","timestamp":1570730956000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/3\/11\/1969\/5554101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,26]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/js.2019-00243","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2019,8,26]]}}}