Novel sequence variation ofAIREand detection of interferon-ω antibodies in early infancy
| Autor: | Anette Bøe Wolff, Margit Zeher, Beáta Tóth, László Maródi, Attila Tar, Zita Halász, Melinda Erdos, István Ilyés, Gyula Szegedi, Péter Szüts, Eystein S. Husebye |
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| Rok vydání: | 2010 |
| Předmět: |
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 |
| Zdroj: | Clinical Endocrinology. 72:641-647 |
| ISSN: | 1365-2265 0300-0664 |
| DOI: | 10.1111/j.1365-2265.2009.03740.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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