Pugliese, AlbertoBoulware, DavidYu, LipingBabu, SunandaSteck, Andrea K.Becker, DorothyRodriguez, HenryDiMeglio, LindaEvans-Molina, CarmellaHarrison, Leonard C.Schatz, DesmondPalmer, Jerry P.Greenbaum, CarlaEisenbarth, George S.Sosenko, Jay M.2020-02-102020-02-102016-04Pugliese, A., Boulware, D., Yu, L., Babu, S., Steck, A. K., Becker, D., … Type 1 Diabetes TrialNet Study Group (2016). 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. Diabetes, 65(4), 1109–1119. doi:10.2337/db15-1105https://hdl.handle.net/1805/22032The 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.en-USPublisher PolicyAutoantibodiesDiabetes ComplicationsDiabetes Mellitus, Type 1Genetic Predisposition to DiseaseHLA-DQ beta-ChainsArticle