Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I

作者：Meloni Antonella; Furcas Maria; Cetani Filomena; Marcocci Claudio; Falorni Alberto; Perniola Roberto; Pura Mikulas; Wolff Anette S Boe; Husebye Eystein S; Lilic Desa; Ryan Kelli R; Gennery Andrew R; Cant Andrew J; Abinun Mario; Spickett Gavin P; Arkwright Peter D; Denning David; Costigan Colm; Dominguez Maria; McConnell Vivienne; Willcox Nick^*; Meager Anthony

来源：Journal of Clinical Endocrinology & Metabolism, 2008, 93(11): 4389-4397.

DOI：10.1210/jc.2008-0935

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: 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.
Design: The study was designed to detect autoantibodies against interferon-alpha 2 and interferon-omega 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-alpha 2 and/or interferon-omega in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-omega, 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. (J Clin Endocrinol Metab 93: 4389-4397, 2008)

• 出版日期2008-11
• 单位河北医科大学