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.
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.
Authors: A S B Wolff; A K Sarkadi; L Maródi; J Kärner; E Orlova; B E V Oftedal; K Kisand; E Oláh; A Meloni; A G Myhre; E S Husebye; R Motaghedi; J Perheentupa; P Peterson; N Willcox; A Meager Journal: J Clin Immunol Date: 2013-10-26 Impact factor: 8.317
Authors: Dong Li; Elizabeth A Streeten; Alice Chan; Wint Lwin; Lifeng Tian; Renata Pellegrino da Silva; Cecilia E Kim; Mark S Anderson; Hakon Hakonarson; Michael A Levine Journal: J Clin Endocrinol Metab Date: 2017-05-01 Impact factor: 5.958
Authors: J Kärner; A Meager; M Laan; J Maslovskaja; M Pihlap; A Remm; E Juronen; A S B Wolff; E S Husebye; K T Podkrajšek; N Bratanic; T Battelino; N Willcox; P Peterson; K Kisand Journal: Clin Exp Immunol Date: 2013-03 Impact factor: 4.330
Authors: S Garelli; M Dalla Costa; C Sabbadin; S Barollo; B Rubin; R Scarpa; S Masiero; A Fierabracci; C Bizzarri; A Crinò; M Cappa; M Valenzise; A Meloni; A M De Bellis; C Giordano; F Presotto; R Perniola; D Capalbo; M C Salerno; A Stigliano; G Radetti; V Camozzi; N A Greggio; F Bogazzi; I Chiodini; U Pagotto; S K Black; S Chen; B Rees Smith; J Furmaniak; G Weber; F Pigliaru; L De Sanctis; C Scaroni; C Betterle Journal: J Endocrinol Invest Date: 2021-05-18 Impact factor: 4.256