Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I

Antonella Meloni, Maria Furcas, Filomena Cetani, Claudio Marcocci, Alberto Falorni, Roberto Perniola, Mikuláš Pura, Anette S. Bøe Wolff, Eystein S. Husebye, Desa Lilic, Kelli R. Ryan, Andrew R. Gennery, Andrew J. Cant, Mario Abinun, Gavin P. Spickett, Peter D. Arkwright, David Denning, Colm Costigan, Maria Dominguez, Vivienne McConnellNick Willcox, Anthony Meager

    Research output: Contribution to journalArticlepeer-review


    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. Objectives: Becausevariability in clinical featuresandageatonsetin APS-I frequently results inunusual 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. Design: The study was designed to detect autoantibodies against interferon-α2 and interferon-ω in antiviral neutralization assays. 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. Outcome: The diagnostic value of anti-interferon autoantibodies was assessed. Results: We found antibodies against interferon-α2 and/or interferon-ω in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-ω, 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. 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. Copyright © 2008 by The Endocrine Society.
    Original languageEnglish
    Pages (from-to)4389-4397
    Number of pages8
    JournalJournal of Clinical Endocrinology and Metabolism
    Issue number11
    Publication statusPublished - Nov 2008


    • blood: Autoantibodies
    • blood: Autoimmune Diseases
    • Diagnosis, Differential
    • Humans
    • genetics: Interferon Type I
    • genetics: Interferon-alpha
    • blood: Myasthenia Gravis
    • Point Mutation
    • blood: Polyendocrinopathies, Autoimmune
    • Sensitivity and Specificity
    • Syndrome
    • immunology: T-Lymphocytes
    • immunology: Thyroid Gland


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