{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:06:57Z","timestamp":1791194817720,"version":"4.1.0"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,2,15]]},"abstract":"<jats:p>Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A\u2013producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and\/ or IL-22 (91%) in &amp;gt;150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.<\/jats:p>","DOI":"10.1084\/jem.20091669","type":"journal-article","created":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T22:05:48Z","timestamp":1265061948000},"page":"299-308","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":619,"title":["Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines"],"prefix":"10.1084","volume":"207","author":[{"given":"Kai","family":"Kisand","sequence":"first","affiliation":[{"name":"Molecular Pathology Group 1 and 2"},{"name":"Immunology Group, Institute of General and Molecular Pathology, University of Tartu, 50411 Tartu, Estonia 1 and 2"},{"name":"Molecular Pathology Group 1 and 2"},{"name":"Immunology Group, Institute of General and Molecular Pathology, University of Tartu, 50411 Tartu, Estonia 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette S.","family":"B\u00f8e Wolff","sequence":"additional","affiliation":[{"name":"Institute of Medicine, University of Bergen 3 and 4"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway 3 and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina Trebu\u0161ak","family":"Podkraj\u0161ek","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics 5 and 6"},{"name":"Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, 1000 Ljubljana, Slovenia 5 and 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liina","family":"Tserel","sequence":"additional","affiliation":[{"name":"Molecular Pathology Group 1 and 2"},{"name":"Immunology Group, Institute of General and Molecular Pathology, University of Tartu, 50411 Tartu, Estonia 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maire","family":"Link","sequence":"additional","affiliation":[{"name":"Molecular Pathology Group 1 and 2"},{"name":"Immunology Group, Institute of General and Molecular Pathology, University of Tartu, 50411 Tartu, Estonia 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle V.","family":"Kisand","sequence":"additional","affiliation":[{"name":"Molecular Pathology Group 1 and 2"},{"name":"Immunology Group, Institute of General and Molecular Pathology, University of Tartu, 50411 Tartu, Estonia 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Ersvaer","sequence":"additional","affiliation":[{"name":"Institute of Medicine, University of Bergen 3 and 4"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway 3 and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Perheentupa","sequence":"additional","affiliation":[{"name":"The Hospital for Children and Adolescents, University of Helsinki, 00290 Helsinki, Finland 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Moter","family":"Erichsen","sequence":"additional","affiliation":[{"name":"Institute of Medicine, University of Bergen 3 and 4"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway 3 and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Bratanic","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics 5 and 6"},{"name":"Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, 1000 Ljubljana, Slovenia 5 and 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Meloni","sequence":"additional","affiliation":[{"name":"Pediatric Clinic II, Ospedale Microcitemico and Department of Biomedical and Biotechnological Science, University of Cagliari, 09121 Cagliari, Italy 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Cetani","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, University of Pisa, 56124 Pisa, Italy 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Perniola","sequence":"additional","affiliation":[{"name":"Department of Paediatrics-Neonatal Intensive Care, V. 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