Novel sequence variation of AIRE and detection of interferon-w antibodies in early infancy

SummaryObjective Autoimmune polyendocrine syndrome type I (APS I) is a rare primary immunodeficiency disorder characterized by chronic mucocutaneous candidiasis, multi-organ autoimmunity and ectodermal dysplasia. Autoantibodies to parathyroid and adrenal glands and type I interferons (IFN) are hallmarks of APS I, which results from mutations in the autoimmune regulator (AIRE) gene. We wished to study clinical, immunological and genetic features of APS I in Hungarian patients, and to correlate anti-IFN-w serum concentration with APS I and other multi-organ autoimmune diseases.Design Detailed analysis of patients with APS I and multi-organ autoimmune diseases.Patients Seven patients with APS I and 11 patients with multi-organ autoimmune diseases were studied.Measurements Mutational analysis was performed by bidirectional sequencing of AIRE. Antibodies against IFN-w and endocrine organ-specific autoantigens were studied with radioimmunoassay. RFLP was performed by digestion of DNA with Hin6I restriction enzyme.Results AIRE sequence analysis revealed homozygous c.769C>T mutations in three patients and compound heterozygous sequence variants (c.769C>T-c.44_66dup26bp; c.769C>T-c.965_977del13bp; c.769C>T-c.1344delC) in four patients with APS I. All the six live patients tested had markedly elevated IFN-w antibodies, which were not found in heterozygous siblings or parents. One of the identified patients was negative for antibodies against IFN-w at 6 weeks of age, but became positive at 7 months. At age 1, he is still without symptoms of the disease. In contrast to patients with APS I, no AIRE mutation or elevation of IFN-w antibodies were detected in patients with multi-organ autoimmune diseases.Conclusion This is the first overview of patients diagnosed with APS I in Hungary. A novel c.1344delC mutation in AIRE was detected. Anti-IFN-w antibodies seem to appear very early in life and are helpful to differentiate APS I from other multi-organ autoimmune diseases.