HLA similarities indicate shared genetic risk in 21‐hydroxylase autoantibody positive South African and United States Addison's disease. Issue 4 (18th July 2014)

• Record Type: Journal Article
• Authors: Ross, I. L.; Babu, S.; Armstrong, T.; Zhang, L.; Schatz, D.; Pugliese, A.; Eisenbarth, G.; Baker II, P.
• Is Part Of: Tissue antigens. Volume 84:Issue 4(2014)
• Page Start: 361
• Page End: 369
• Publication Date: 2014-07-18
• Subjects: Antigens -- Periodicals; Immunological tolerance -- Periodicals; Immunogenetics -- Periodicals; 571.9645
• DOI: 10.1111/tan.12407
• Languages: English
• ISSNs: 0001-2815

Abstract

<abstract abstract-type="main" id="tan12407-abs-0001"> <title>Abstract</title> <p id="tan12407-para-0001">Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA‐AD (<italic>n</italic> = 73), SA healthy controls (<italic>N</italic> = 78), and US‐AD patients (<italic>N</italic> = 83) were genotyped for DQA1, DQB1, DRB1, and HLA‐B alleles. Serum was tested for the quantity of 21OH‐AA and IFNα‐AA at the Barbara Davis Center. Although not as profound as in US‐AD, in SA‐AD 21OH‐AA + subjects the predominantly associated risk haplotypes were <italic>DRB1*0301‐DQB1*0201</italic> (DR3), <italic>DRB1*04xx‐DQB1*0302</italic> (DR4), and the combined DR3/4 genotype. <italic>DQB1*0302</italic> associated <italic>DRB1*04xx</italic> haplotypes conferred higher risk than those <italic>DRB1*04xx</italic> haplotypes associated with other DQB1 alleles. We found negative association in 21OH‐AA + SA‐AD for <italic>DQA1*0201‐DQB1*0202</italic> and <italic>DQA1*0101‐DQB1*0501 vs</italic> SA controls, and positive association for <italic>DQA1*0401‐DQB1*0402 vs</italic> US‐AD. Apart from the class II DR3 haplotype, HLA‐B8 did not have an independent effect; however together DR3 and HLA‐B8 conferred the highest risk <italic>vs</italic> 21OH‐AA negative SA‐AD and SA‐controls. HLA‐B7 (often with DR4) conferred novel risk in 21OH‐AA + SA‐AD <italic>vs</italic> controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA‐AD and US‐AD 21OH‐AA + patients share common HLA risk haplotypes including DR4 (with HLA‐B7) and DR3 (with HLA‐B8), strengthening previously described HLA associations and implicating similar genetic etiology.</p> </abstract>