{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:24:33Z","timestamp":1791465873283,"version":"4.3.4"},"reference-count":44,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,11,1]]},"abstract":"<jats:p>Context: In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations.<\/jats:p>\n                  <jats:p>Objectives: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation.<\/jats:p>\n                  <jats:p>Design: The study was designed to detect autoantibodies against interferon-\u03b12 and interferon-\u03c9 in antiviral neutralization assays.<\/jats:p>\n                  <jats:p>Setting and Patients: Patients included 14 British\/Irish, 15 Sardinian, and 10 Southern Italian AIRE-mutant patients with APS-I; also 19 other patients with CMC, including four families with cosegregating thyroid autoimmunity.<\/jats:p>\n                  <jats:p>Outcome: The diagnostic value of anti-interferon autoantibodies was assessed.<\/jats:p>\n                  <jats:p>Results: We found antibodies against interferon-\u03b12 and\/or interferon-\u03c9 in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British\/Irish CMC patients. Especially against interferon-\u03c9, titers were nearly always high, regardless of the exact APS-I phenotype\/duration or AIRE genotype, including 12 different AIRE length variants or 10 point substitutions overall (n = 174 total). Strikingly, in one family with few typical APS-I features, these antibodies cosegregated over three generations with autoimmune hypothyroidism plus a dominant-negative G228W AIRE substitution.<\/jats:p>\n                  <jats:p>Conclusions: Otherwise restricted to patients with thymoma and\/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.<\/jats:p>","DOI":"10.1210\/jc.2008-0935","type":"journal-article","created":{"date-parts":[[2008,8,26]],"date-time":"2008-08-26T20:44:41Z","timestamp":1219783481000},"page":"4389-4397","source":"Crossref","is-referenced-by-count":185,"title":["Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I"],"prefix":"10.1210","volume":"93","author":[{"given":"Antonella","family":"Meloni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Furcas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Cetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Marcocci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Falorni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Perniola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikula\u0301s\u030c","family":"Pura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette S.","family":"B\u00f8e Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eystein S.","family":"Husebye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desa","family":"Lilic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli R.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Gennery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Cant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Abinun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin P.","family":"Spickett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Arkwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Denning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm","family":"Costigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivienne","family":"McConnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Willcox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Meager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613411321100_R1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0889-8529(01)00013-5","article-title":"APS-I\/APECED: the clinical disease and therapy.","volume":"31","author":"Perheentupa","year":"2002","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071613411321100_R2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nri2136","article-title":"A decade of AIRE.","volume":"7","author":"Mathis","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"2020071613411321100_R3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng1297-393","article-title":"Positional cloning of the APECED gene.","volume":"17","author":"Nagamine","year":"1997","journal-title":"Nat Genet"},{"key":"2020071613411321100_R4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ng1297-399","article-title":"An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy.","volume":"17","author":"The Finnish-German APECED consortium","year":"1997","journal-title":"Nat Genet"},{"key":"2020071613411321100_R5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/ng0397-289","article-title":"Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus.","volume":"15","author":"Vafiadis","year":"1997","journal-title":"Nat Genet"},{"key":"2020071613411321100_R6","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1126\/science.1075958","article-title":"Projection of an immunological self shadow within the thymus by the aire protein.","volume":"298","author":"Anderson","year":"2002","journal-title":"Science"},{"key":"2020071613411321100_R7","first-page":"515","article-title":"Polyendocrine syndromes","author":"Peterson","year":"2006","journal-title":"In Rose N, Mackay IR, eds. The autoimmune diseases. 4th ed. 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