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: Maria Halonen, Petra Eskelin, Anne-Grethe Myhre, Jaakko Perheentupa, Eystein S Husebye, Olle Kämpe, Fredrik Rorsman, Leena Peltonen, Ismo Ulmanen, Jukka Partanen
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 87 Issue 6 Pg. 2568-74 (Jun 2002) ISSN: 0021-972X [Print] United States
• PMID: 12050215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APECED protein
• Autoantibodies
• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• HLA-DR Antigens
• HLA-DRB1 Chains
• Transcription Factors

Topics

• Adolescent
• Adult
• Autoantibodies (analysis)
• Child
• Genotype
• HLA-DQ Antigens (analysis)
• HLA-DQ beta-Chains
• HLA-DR Antigens (analysis, immunology)
• HLA-DRB1 Chains
• Humans
• Middle Aged
• Mutation
• Phenotype
• Polyendocrinopathies, Autoimmune (genetics, immunology)
• Transcription Factors (genetics)