HLA-DRB115:01-DQA101:02-DQB106:02 haplotype protects autoantibody-positive relatives from type 1 diabetes throughout the stages of disease progression

Alberto Pugliese, David Boulware, Liping Yu, Sunanda Babu, Andrea K. Steck, Dorothy Becker, Henry Rodriguez, Linda Di Meglio, Carmella Evans-Molina, Leonard C. Harrison, Desmond Schatz, Jerry P. Palmer, Carla Greenbaum, George S. Eisenbarth, Jay M. Sosenko

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The HLA-DRB115:01-DQA101:02-DQB106:02 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 DRB115:01-DQA101:02-DQB106:02 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 DRB115:01-DQA101:02-DQB106:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D.

Original languageEnglish (US)
Pages (from-to)1109-1119
Number of pages11
Issue number4
StatePublished - Apr 2016

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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