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

Ye, Jody, Long, Anna E., Pearson, James A., Taylor, Hazel, Bingley, Polly J., Williams, Alistair J. K. and Gillespie, Kathleen M. 2015. Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes. Diabetologia 58 (10) , pp. 2284-2287. 10.1007/s00125-015-3702-9

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Springer Verlag
ISSN: 0012-186X
Date of Acceptance: 29 June 2015
Last Modified: 13 May 2020 15:02
URI: http://orca-mwe.cf.ac.uk/id/eprint/131614

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