1. Novel sequence variation ofAIREand detection of interferon-ω antibodies in early infancy
- Author
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Anette Bøe Wolff, Margit Zeher, Beáta Tóth, László Maródi, Attila Tar, Zita Halász, Melinda Erdos, István Ilyés, Gyula Szegedi, Péter Szüts, and Eystein S. Husebye
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,Endocrinology, Diabetes and Metabolism ,DNA Mutational Analysis ,Radioimmunoassay ,medicine.disease_cause ,Compound heterozygosity ,Autoimmunity ,Young Adult ,Endocrinology ,Internal medicine ,Humans ,Medicine ,Chronic mucocutaneous candidiasis ,Child ,Polyendocrinopathies, Autoimmune ,Aged ,Autoantibodies ,Family Health ,Polymorphism, Genetic ,Base Sequence ,biology ,business.industry ,Age Factors ,Autoantibody ,Infant ,Middle Aged ,medicine.disease ,Autoimmune regulator ,Pedigree ,Autoimmune polyendocrine syndrome ,Interferon Type I ,Mutation ,Immunology ,biology.protein ,Primary immunodeficiency ,Female ,Antibody ,business ,Polymorphism, Restriction Fragment Length ,Transcription Factors - Abstract
Objective 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-omega 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-omega 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-omega antibodies, which were not found in heterozygous siblings or parents. One of the identified patients was negative for antibodies against IFN-omega 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-omega 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-omega antibodies seem to appear very early in life and are helpful to differentiate APS I from other multi-organ autoimmune diseases.
- Published
- 2010