title: AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype.
abstract: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, OMIM 240300) is a rare autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21q22.3. This monogenic disease provides an interesting model for studies of other common and more complex autoimmune diseases. The most common components of APECED are chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease, but several other endocrine deficiencies and ectodermal dystrophies also occur and the phenotype varies widely. The AIRE genotype also varies; 42 different mutations have been reported so far. To understand the complexity of the phenotype, we studied the AIRE and human leukocyte antigen (HLA) class II genotypes in a series of patients with APECED. The only association between the phenotype and the AIRE genotype was the higher prevalence of candidiasis in the patients with the most common mutation, R257X, than in those with other mutations. Addison's disease was associated with HLA-DRB1*03 (P = 0.021), alopecia with HLA-DRB1*04- DQB1*0302 (P < 0.001), whereas type 1 diabetes correlated negatively with HLA-DRB1*15-DQB1*0602 (P = 0.036). The same HLA associations have previously been established for non-APECED patients. We conclude that mutation of AIRE per se has little influence on the APECED phenotype, whereas, in contrast to earlier reports, HLA class II is a significant determinant.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Biomedicum, Haartmaninkatu 8, FIN-00290 Helsinki, Finland. maria.halonen@ktl.fi
authors.forename: Maria
authors.initials: M
authors.lastname: Halonen
authors.forename: Petra
authors.initials: P
authors.lastname: Eskelin
authors.forename: Anne-Grethe
authors.initials: AG
authors.lastname: Myhre
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rorsman
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Ismo
authors.initials: I
authors.lastname: Ulmanen
authors.forename: Jukka
authors.initials: J
authors.lastname: Partanen
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D002648:Child; D005838:Genotype; D006683:HLA-DQ Antigens / Q000032:analysis; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014157:Transcription Factors; D000096927:AIRE Protein; C069051:HLA-DQB1 antigen