Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes

Jody Ye, Anna E. Long, James A. Pearson, Hazel Taylor, Polly J. Bingley, Alistair J.K. Williams, Kathleen M. Gillespie

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Aims/hypothesis: The rate of progression from islet autoimmunity to clinical type 1 diabetes depends on the rate of beta cell destruction. The HLA-A*24 gene is associated with early diabetes onset, but previous studies have shown attenuated humoral responses to islet antigens in individuals with both recent and long-standing type 1 diabetes carrying HLA-A*24. We aimed to establish whether HLA-A*24 is also associated with attenuated humoral responses in individuals at high risk of type 1 diabetes. Methods: We established HLA-A*24, DQ and rs9258750 (an HLA-A*24 tagged single-nucleotide polymorphism) genotype, as well as GAD, zinc transporter 8 (ZnT8), insulin, islet antigen-2 (IA-2), and IA-2β autoantibody status in 373 islet cell antibody-positive first-degree relatives participating in the European Nicotinamide Diabetes Intervention Trial. Results: Univariate regression analyses showed that humoral responses to GAD, ZnT8 and insulin were less common in relatives carrying HLA-A*24. The prevalence of GAD and ZnT8 autoantibodies remained negatively associated with HLA-A*24 and rs9258750 after adjusting for age, sex, proband relationship and HLA class II genotype. Conclusions/interpretation: HLA-A*24 is associated with attenuated humoral responses in individuals at high risk of type 1 diabetes, and this may reflect a distinct phenotype of rapid beta cell loss.

Original languageEnglish (US)
Pages (from-to)2284-2287
Number of pages4
JournalDiabetologia
Volume58
Issue number10
DOIs
StatePublished - Oct 24 2015
Externally publishedYes

Keywords

  • Autoantibodies
  • HLA-A*24
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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