Autoantibodies to islet antigen-2 are associated with HLA-DRB1*07 and DRB1*09 haplotypes as well as DRB1*04 at onset of type 1 diabetes: The possible role of HLA-DQA in autoimmunity to IA-2

A. J K Williams, R. J. Aitken, M. A M Chandler, K. M. Gillespie, V. Lampasona, P. J. Bingley

Research output: Contribution to journalArticle

Abstract

Aims/hypothesis: To further our understanding of antigen presentation by HLA class II molecules, we have examined the influence of HLA class II genotype on expression of autoantibodies to islet antigen-2 (IA-2A). Methods: HLA class II genotype and IA-2A were determined within 3 months of diagnosis in 618 patients with type 1 diabetes (median age 11 years [range 0.7-20.9]). Antibodies to the juxtamembrane region of IA-2 were measured by a radiobinding assay in 481 of 484 IA-2A-positive patients. Results: IA-2A prevalence was highest in patients carrying at least one HLA-DRB1*04-DQA1*0301 (385 of 450; 86%), DRB1*07-DQA1*(0201 or 0301) (58 of 64; 91%) or DRB1*09-DQA1*0301 haplotype (18 of 19; 95%). Multiple regression showed that IA-2A were strongly associated with the number of these haplotypes carried; only 69 of 132 (52%) patients carrying none of these haplotypes had IA-2A, compared with 322 of 391 (82%) patients with one and 93 of 95 (98%) with two of these haplotypes (p

Original languageEnglish
Pages (from-to)1444-1448
Number of pages5
JournalDiabetologia
Volume51
Issue number8
DOIs
Publication statusPublished - Aug 2008

Keywords

  • HLA class II
  • IA-2 autoantibodies
  • Juxtamembrane antibodies
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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