{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:36:59Z","timestamp":1791005819471,"version":"4.1.0"},"reference-count":44,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thematic Excellence Program 2021","award":["RRF-2.3.1-21-2022-00012"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The purpose of our work was to provide a data-driven perspective to autoimmune polyglandular syndrome (APS), a complex autoimmune disorder, supplementing traditional clinical observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Medical records of 7559 patients were analyzed, and autoimmune origin was proved in 3180 cases of which 380 (12%) had APS. Associations of component disorders were investigated by computational methods to reveal typical patterns of disease development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-eight distinct autoimmune disorders were diagnosed forming 113 combinations. The 10 most frequent combinations were responsible for 51.3% of cases. Hashimoto's thyroiditis (HT) and Graves\u2019 disease (GD) were differentiated as the main cornerstones of APS, sharing several comorbidities. HT was the most common manifestation (67.4%), followed by GD (26.8%) and type 1 diabetes mellitus (T1D) (20.8%). APS started significantly earlier in men than in women. Thyroid autoimmunity was frequently linked to gastrointestinal and systemic manifestations, and these patterns of associations substantially differed from that of T1D, Addison\u2019s disease, or coeliac disease when present as first manifestations, suggesting the possibility of a common biological cause.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>APS is more frequent than reported. Classifying APS requires a shift of perspective toward disease associations rather than disorder prevalence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae701","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T07:21:30Z","timestamp":1728026490000},"page":"1716-1728","source":"Crossref","is-referenced-by-count":6,"title":["Systematic Analysis and Network Mapping of Disease Associations in Autoimmune Polyglandular Syndrome"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1578-1312","authenticated-orcid":false,"given":"Greta","family":"Pham-Dobor","sequence":"first","affiliation":[{"name":"First Department of Medicine, Clinical Centre, Medical School, University of Pecs , Pecs 7624 ,","place":["Hungary"]},{"name":"Institute For Translational Medicine, Medical School, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kaltenecker","sequence":"additional","affiliation":[{"name":"Szentagothai Research Centre, University of Pecs , Pecs 7624 ,","place":["Hungary"]},{"name":"National Laboratory on Human Reproduction, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Temesfoi","sequence":"additional","affiliation":[{"name":"Szentagothai Research Centre, University of Pecs , Pecs 7624 ,","place":["Hungary"]},{"name":"National Laboratory on Human Reproduction, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Bajnok","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Clinical Centre, Medical School, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya","family":"Nemes","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Clinical Centre, Medical School, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Bodis","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Clinical Centre, Medical School, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-3877","authenticated-orcid":false,"given":"Emese","family":"Mezosi","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Clinical Centre, Medical School, University of Pecs , Pecs 7624 ,","place":["Hungary"]},{"name":"Szentagothai Research Centre, University of Pecs , Pecs 7624 ,","place":["Hungary"]},{"name":"National Laboratory on Human Reproduction, University of Pecs , Pecs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"issue":"10","key":"2025052712550160300_dgae701-B1","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1210\/jc.2019-00602","article-title":"Autoimmune polyendocrinopathy","volume":"104","author":"Frommer","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025052712550160300_dgae701-B2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s12022-023-09771-3","article-title":"Inflammatory and infectious disorders in endocrine pathology","volume":"34","author":"Uccella","year":"2023","journal-title":"Endocr Pathol"},{"issue":"9","key":"2025052712550160300_dgae701-B3","doi-asserted-by":"crossref","first-page":"1\u2013","DOI":"10.1007\/s40618-020-01229-1","article-title":"Prevalence of other autoimmune diseases in polyglandular autoimmune syndromes type II and III","volume":"43","author":"Pham-Dobor","year":"2020","journal-title":"J Endocrinol Invest"},{"issue":"2","key":"2025052712550160300_dgae701-B4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1365-2249.2004.02561.x","article-title":"Autoimmune polyglandular syndrome type 2: the tip of an iceberg?","volume":"137","author":"Betterle","year":"2004","journal-title":"Clin Exp Immunol"},{"issue":"November","key":"2025052712550160300_dgae701-B5","doi-asserted-by":"crossref","first-page":"1274672","DOI":"10.3389\/fimmu.2023.1274672","article-title":"A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review","volume":"14","author":"Sapana","year":"2023","journal-title":"Front Immunol"},{"issue":"1","key":"2025052712550160300_dgae701-B6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/BF03401285","article-title":"Thyroid autoimmunity and polyglandular endocrine syndromes","volume":"12","author":"W\u00e9meau","year":"2013","journal-title":"Hormones"},{"issue":"3","key":"2025052712550160300_dgae701-B7","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1177\/1721727X1301100329","article-title":"Hashimoto's thyroiditis and entero-chromaffin-like cell hyperplasia: early detection and somatostatin analogue treatment","volume":"11","author":"Renzullo","year":"2013","journal-title":"Eur J Inflamm"},{"key":"2025052712550160300_dgae701-B8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1136\/bcr-2015-210506","article-title":"Addison's disease in a patient with hypothyroidism: autoimmune polyglandular syndrome type 2","volume":"2015","author":"Bain","year":"2015","journal-title":"BMJ Case Rep"},{"issue":"2","key":"2025052712550160300_dgae701-B9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.autrev.2013.07.006","article-title":"Autoimmune polyendocrine syndromes","volume":"13","author":"Cutolo","year":"2014","journal-title":"Autoimmun Rev"},{"issue":"October","key":"2025052712550160300_dgae701-B10","doi-asserted-by":"crossref","first-page":"1236878\u2013","DOI":"10.3389\/fendo.2023.1236878","article-title":"Autoimmune polyglandular syndrome type 4: experience from a single reference center","volume":"14","author":"Gatta","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2025052712550160300_dgae701-B11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40618-017-0740-9","article-title":"Polyglandular autoimmune syndromes","volume":"41","author":"Kahaly","year":"2018","journal-title":"J Endocrinol Invest"},{"issue":"4","key":"2025052712550160300_dgae701-B12","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s40618-022-01994-1","article-title":"Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy","volume":"46","author":"Betterle","year":"2023","journal-title":"J Endocrinol Invest"},{"issue":"5","key":"2025052712550160300_dgae701-B13","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/j.1365-2230.2006.02171.x","article-title":"Vitiligo associated with other autoimmune diseases: polyglandular autoimmune syndrome types 3B + C and 4","volume":"31","author":"Amerio","year":"2006","journal-title":"Clin Exp Dermatol"},{"issue":"6","key":"2025052712550160300_dgae701-B14","doi-asserted-by":"crossref","first-page":"101344","DOI":"10.1016\/j.beem.2019.101344","article-title":"Autoimmune polyglandular diseases","volume":"33","author":"Kahaly","year":"2019","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"Patient 1","key":"2025052712550160300_dgae701-B15","doi-asserted-by":"crossref","first-page":"11795514211009796","DOI":"10.1177\/11795514211009796","article-title":"Search for genetic predictors of adult autoimmune polyendocrine syndrome in monozygotic twins","volume":"14","author":"Yukina","year":"2021","journal-title":"Clin Med Insights Endocrinol Diabetes"},{"issue":"3","key":"2025052712550160300_dgae701-B16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1568-9972(03)00006-5","article-title":"The epidemiology of autoimmune diseases","volume":"2","author":"Cooper","year":"2003","journal-title":"Autoimmun Rev"},{"issue":"4-5","key":"2025052712550160300_dgae701-B17","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.autrev.2014.01.049","article-title":"The diagnosis and clinical significance of polyautoimmunity","volume":"13","author":"Anaya","year":"2014","journal-title":"Autoimmun Rev"},{"issue":"9372","key":"2025052712550160300_dgae701-B18","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/S0140-6736(03)13492-7","article-title":"Adrenal insufficiency","volume":"361","author":"Arlt","year":"2003","journal-title":"Lancet"},{"issue":"3","key":"2025052712550160300_dgae701-B19","first-page":"1","article-title":"Autoimmune polyendocrine syndromes in the pediatric age","volume":"10","author":"Paparella","year":"2023","journal-title":"Children (Basel, Switzerland)"},{"issue":"4","key":"2025052712550160300_dgae701-B20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1399-0039.2011.01634.x","article-title":"Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes","volume":"77","author":"Weinstock","year":"2011","journal-title":"Tissue Antigens"},{"issue":"1","key":"2025052712550160300_dgae701-B21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4239\/wjd.v6.i1.67","article-title":"Type 1 diabetes and polyglandular autoimmune syndrome: a review","volume":"6","author":"Hansen","year":"2015","journal-title":"World J Diabetes"},{"issue":"5","key":"2025052712550160300_dgae701-B22","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1210\/jc.2017-02577","article-title":"PTPN22 and CTLA-4 polymorphisms are associated with polyglandular autoimmunity","volume":"103","author":"Houcken","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"issue":"168","key":"2025052712550160300_dgae701-B23","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.lfs.2017.11.026","article-title":"Autoimmune thyroid diseases and Th17\/Treg lymphocytes","volume":"192","author":"Shao","year":"2018","journal-title":"Life Sci"},{"issue":"11","key":"2025052712550160300_dgae701-B24","doi-asserted-by":"crossref","first-page":"5502","DOI":"10.3390\/ijms22115502","article-title":"Multiplex autoantibody detection in patients with autoimmune polyglandular syndromes","volume":"22","author":"Savvateeva","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"2","key":"2025052712550160300_dgae701-B25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000369535","article-title":"Celiac disease and endocrine autoimmunity","volume":"33","author":"Kahaly","year":"2015","journal-title":"Digestive Diseases"},{"issue":"1","key":"2025052712550160300_dgae701-B26","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s12020-021-02743-9","article-title":"Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity","volume":"74","author":"Fichna","year":"2021","journal-title":"Endocrine"},{"issue":"4","key":"2025052712550160300_dgae701-B27","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1210\/jc.2005-1679","article-title":"Type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening","volume":"91","author":"Barker","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2025052712550160300_dgae701-B28","author":"Kaltenecker","year":"2024"},{"issue":"11","key":"2025052712550160300_dgae701-B29","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/spe.4380211102","article-title":"Graph drawing by force-directed placement","volume":"21","author":"Fruchterman","year":"1991","journal-title":"Softw Pract Exp"},{"issue":"10","key":"2025052712550160300_dgae701-B30","doi-asserted-by":"crossref","first-page":"P10008","DOI":"10.1088\/1742-5468\/2008\/10\/P10008","article-title":"Fast unfolding of communities in large networks","volume":"2008","author":"Blondel","year":"2008","journal-title":"J Stat Mech"},{"issue":"8","key":"2025052712550160300_dgae701-B31","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.2337\/diacare.25.8.1346","article-title":"Thyroid autoimmunity in children and adolescents with type 1 diabetes","volume":"25","author":"Kordonouri","year":"2002","journal-title":"Diabetes Care"},{"issue":"4","key":"2025052712550160300_dgae701-B32","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s004150170210","article-title":"Polyglandular autoimmune syndrome type II and multiple sclerosis","volume":"248","author":"Sastre-Garriga","year":"2001","journal-title":"J Neurol"},{"issue":"7","key":"2025052712550160300_dgae701-B33","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.autrev.2016.02.017","article-title":"Type 1 diabetes associated autoimmunity","volume":"15","author":"Kahaly","year":"2016","journal-title":"Autoimmun Rev"},{"issue":"7","key":"2025052712550160300_dgae701-B34","doi-asserted-by":"crossref","first-page":"814","DOI":"10.3390\/nu10070814","article-title":"Celiac disease and glandular autoimmunity","volume":"10","author":"Kahaly","year":"2018","journal-title":"Nutrients"},{"issue":"1","key":"2025052712550160300_dgae701-B35","first-page":"9","article-title":"Update on autoimmune polyendocrine syndromes (APS)","volume":"74","author":"Betterle","year":"2003","journal-title":"Acta Biomed"},{"issue":"12","key":"2025052712550160300_dgae701-B36","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1007\/s00125-002-0923-5","article-title":"Severe clinical onset of diabetes and increased prevalence of other autoimmune diseases in children with coeliac disease diagnosed before diabetes mellitus","volume":"45","author":"Valerio","year":"2002","journal-title":"Diabetologia"},{"issue":"10115","key":"2025052712550160300_dgae701-B37","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0140-6736(17)31796-8","article-title":"Coeliac disease","volume":"391","author":"Lebwohl","year":"2018","journal-title":"Lancet"},{"issue":"1","key":"2025052712550160300_dgae701-B38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0054-z","article-title":"Coeliac disease","volume":"5","author":"Lindfors","year":"2019","journal-title":"Nat Rev Dis Primers"},{"issue":"7","key":"2025052712550160300_dgae701-B39","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1055\/a-0653-7108","article-title":"The effect of gluten-free diet on thyroid autoimmunity in drug-na\u00efve women with Hashimoto's thyroiditis: a pilot study","volume":"127","author":"Krysiak","year":"2019","journal-title":"Exp Clin Endocrinol Diabetes"},{"issue":"2","key":"2025052712550160300_dgae701-B40","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jaad.2014.03.017","article-title":"Diet and psoriasis, part II: celiac disease and role of a gluten-free diet","volume":"71","author":"Bhatia","year":"2014","journal-title":"J Am Acad Dermatol"},{"issue":"8","key":"2025052712550160300_dgae701-B41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/nu12082316","article-title":"Current evidence on the efficacy of gluten-free diets in multiple sclerosis, psoriasis, type 1 diabetes and autoimmune thyroid diseases","volume":"12","author":"Passali","year":"2020","journal-title":"Nutrients"},{"issue":"6","key":"2025052712550160300_dgae701-B42","doi-asserted-by":"crossref","first-page":"101497","DOI":"10.1016\/j.berh.2020.101497","article-title":"The microbiome and rheumatoid arthritis","volume":"33","author":"Bergot","year":"2019","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"1","key":"2025052712550160300_dgae701-B43","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/cei.13158","article-title":"The microbiome in autoimmune diseases","volume":"195","author":"De Luca","year":"2019","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"2025052712550160300_dgae701-B44","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1136\/gut.37.3.447","article-title":"Coeliac disease and autoimmune thyroid disease [6]","volume":"37","author":"Weissel","year":"1995","journal-title":"Gut"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgae701\/60182646\/dgae701.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/6\/1716\/60182646\/dgae701.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/6\/1716\/60182646\/dgae701.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:55:14Z","timestamp":1748350514000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/6\/1716\/7815758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,10,8]]},"published-print":{"date-parts":[[2025,5,19]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgae701","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2024,10,8]]}}}