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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

Authors :
Desmond A. Schatz
Sunanda R. Babu
Jay M. Sosenko
Leonard C. Harrison
Jerry P. Palmer
Alberto Pugliese
Carla J. Greenbaum
David Boulware
Liping Yu
Linda A. Dimeglio
Andrea K. Steck
Henry Rodriguez
Dorothy J. Becker
George S. Eisenbarth
Carmella Evans-Molina
Source :
Diabetes
Publication Year :
2016
Publisher :
American Diabetes Association, 2016.

Abstract

The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the 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 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 DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D.

Details

ISSN :
1939327X and 00121797
Volume :
65
Database :
OpenAIRE
Journal :
Diabetes
Accession number :
edsair.doi.dedup.....a178fbc23732a91c019563486a84e5d4
Full Text :
https://doi.org/10.2337/db15-1105