{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:15:12Z","timestamp":1761920112228,"version":"3.38.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoimmune polyendocrinopathy\u2013candidiasis\u2013ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p &amp;lt; 0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti\u2013IL-17 or \u2013IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti\u2013S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO+ population (\u03c1 = \u22120.706; p &amp;lt; 0.01). APECED patients also had decreased numbers of FOXP3+ cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn\u2019s disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.<\/jats:p>","DOI":"10.4049\/jimmunol.1500301","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T04:13:29Z","timestamp":1456200809000},"page":"2955-2964","source":"Crossref","is-referenced-by-count":14,"title":["Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy\u2013Candidiasis\u2013Ectodermal Dystrophy Patients"],"prefix":"10.1093","volume":"196","author":[{"given":"Iivo","family":"Hetem\u00e4ki","sequence":"first","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki , 00290 Helsinki ,","place":["Finland"]},{"name":"Research Programs Unit, Immunobiology Research Program, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Jarva","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki , 00290 Helsinki ,","place":["Finland"]},{"name":"Research Programs Unit, Immunobiology Research Program, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"HUSLAB, Helsinki University Central Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Kluger","sequence":"additional","affiliation":[{"name":"Department of Skin and Allergic Diseases, Skin and Allergy Hospital, Helsinki University Central Hospital , 00250 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-697X","authenticated-orcid":false,"given":"Hanna-Mari","family":"Baldauf","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-2849","authenticated-orcid":false,"given":"Sini","family":"Laakso","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8359-9818","authenticated-orcid":false,"given":"Eirik","family":"Bratland","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haukeland University Hospital , 5021 Bergen ,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eystein S","family":"Husebye","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haukeland University Hospital , 5021 Bergen ,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Kisand","sequence":"additional","affiliation":[{"name":"Institute of General and Molecular Pathology, University of Tartu , Tartu 50411 ,","place":["Estonia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamari","family":"Ranki","sequence":"additional","affiliation":[{"name":"Department of Skin and Allergic Diseases, Skin and Allergy Hospital, Helsinki University Central Hospital , 00250 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e4rt","family":"Peterson","sequence":"additional","affiliation":[{"name":"Institute of General and Molecular Pathology, University of Tartu , Tartu 50411 ,","place":["Estonia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T Petteri","family":"Arstila","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki , 00290 Helsinki ,","place":["Finland"]},{"name":"Research Programs Unit, Immunobiology Research Program, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"2025030702152108600_r1","first-page":"15","article-title":"Autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED)\u2014a diagnostic and therapeutic challenge","volume":"7","author":"J\u00e4\u00e4skel\u00e4inen","year":"2009","journal-title":"Pediatr. 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