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The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype protects autoantibody-positive relatives from type 1 diabetes throughout the stages of disease progression


Pugliese, A; Boulware, D; Yu, L; Babu, S; Steck, AK; Becker, D; Rodriguez, H; DiMeglio, L; Evans-Molina, C; Harrison, LC; Schatz, D; Palmer, JP; Greenbaum, C; Eisenbarth, GS; Sosenko, JM; Type 1 Diabetes TrialNet Study, Group
2016-01-28
Diabetes
Journal Article in press
The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA-typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow-up. These relatives also had lower frequencies of metabolic abnormalities at baseline, and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of the DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D.
American Diabetes Association
Population Health and Immunity
10.2337/db15-1105
26822082
Refer to copyright notice on published article.

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Creation Date 2016-03-14 03:05:31 Last Modified 2016-03-14 03:48:06