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 language | English |
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Pages (from-to) | 2284-7 |
Number of pages | 4 |
Journal | Diabetologia |
Volume | 58 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 2015 |
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Professor Kathleen M Gillespie
- Bristol Medical School (THS) - Professor of Molecular Medicine
- Bristol Population Health Science Institute
- Infection and Immunity
- Diabetes and Metabolism
Person: Academic , Member
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Dr Anna E Long
- Bristol Medical School (THS) - Lecturer in Diabetes
- Infection and Immunity
- Diabetes and Metabolism
Person: Academic , Member