{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:56:12Z","timestamp":1793094972385,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T00:00:00Z","timestamp":1464134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Eesti Teadusagentuur","doi-asserted-by":"publisher","award":["IUT2\u20102"],"award-info":[{"award-number":["IUT2\u20102"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008369","name":"Archimedes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008369","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Both autoimmune polyendocrinopathy\u2010candidiasis\u2010ectodermal dystrophy (APECED) and the rare thymoma patients with chronic mucocutaneous candidiasis (CMC) have neutralizing autoantibodies to Th17 cytokines and significant defects in production of IL\u201022 and IL\u201017F by their T cells. The cause of these defects is unknown. We hypothesized that they might result from autoimmunity against upstream cytokines normally responsible for generating and maintaining Th17 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Luciferase immunoprecipitation (LIPS) was used to screen for autoantibodies to IL\u20106, IL\u20101\u03b2, TGF\u2010\u03b23, IL\u201021, and IL\u201023 in patients with APECED or thymoma. We used Western blotting to assess the conformation\u2010dependence of the IL\u20106 autoantibodies and flow cytometric analysis of intracellular phospho\u2010STAT3 induction to assess IL\u20106\u2010neutralizing capacity in IgGs isolated from patient and control sera. We also used Luminex xMAP to measure serum cytokine levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found autoantibodies binding to conformational epitopes of IL\u20106 in 19.5% of 41 patients with APECED and 12.5% of 104 with thymoma\u2014especially in those with long disease durations. The autoantibodies were predominantly of IgG1 subclass and failed to neutralize IL\u20106 activity. Notably, serum levels of the IL\u20106 and IL\u201017A cytokines were higher in anti\u2010IL\u20106 seropositive than\u2014negative APECED patients or healthy controls. We also detected autoantibody binding to IL\u201023 in 27.9% of thymoma patients, resulting from cross\u2010recognition through the p40 subunit it shares with IL\u201012.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IL\u20106 and IL\u201017A elevation in these seropositive patients suggests that antibody\u2010binding may protect IL\u20106 from degradation and prolong its half\u2010life in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.109","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T10:06:24Z","timestamp":1464170784000},"page":"235-243","source":"Crossref","is-referenced-by-count":41,"title":["IL\u20106\u2010specific autoantibodies among APECED and thymoma patients"],"prefix":"10.1002","volume":"4","author":[{"given":"Jaanika","family":"K\u00e4rner","sequence":"first","affiliation":[{"name":"Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maire","family":"Pihlap","sequence":"additional","affiliation":[{"name":"Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamari","family":"Ranki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, and Skin and Allergy Hospital Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Krohn","sequence":"additional","affiliation":[{"name":"Clinical Research Institute HUCH Ltd. Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Trebusak Podkrajsek","sequence":"additional","affiliation":[{"name":"Unit for Special Laboratory Diagnostics, University Children's Hospital University Medical Centre Ljubljana Slovenia"},{"name":"University of Ljubljana, Medical Faculty Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Bratanic","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Diabetes and Metabolism University Children's Hospital, University Medical Centre Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadej","family":"Battelino","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Diabetes and Metabolism University Children's Hospital, University Medical Centre Ljubljana Slovenia"},{"name":"University of Ljubljana, Medical Faculty Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Willcox","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine University of Oxford Oxford OX3 9DS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4rt","family":"Peterson","sequence":"additional","affiliation":[{"name":"Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kisand","sequence":"additional","affiliation":[{"name":"Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4769"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/380453"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.1.647"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202526"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-013-9908-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091669"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091983"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401068"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2009.01454.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-393"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-399"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181f1f63f"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2014.929666"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.08.027"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939883"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.01.001"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.04.005"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100114"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.06.020"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2003.02113.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12024"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-286161"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)64012-3"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(03)00136-X"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030289"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.07.032"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082767"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425268"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1991.tb02552.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0176-y"},{"key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.4049\/jimmunol.152.2.935","article-title":"IL\u20106\u2010anti\u2010IL\u20106 autoantibody complexes with IL\u20106 activity in sera from some patients with systemic sclerosis","volume":"152","author":"Suzuki H.","year":"1994","journal-title":"J. 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