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 journalArticle

16 Citations (Scopus)

Abstract

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
JournalDiabetes
Volume65
Issue number4
DOIs
StatePublished - Apr 1 2016

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Type 1 Diabetes Mellitus
Autoantibodies
Haplotypes
Disease Progression
Histocompatibility Testing
Alleles
Incidence

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

HLA-DRB115 : 01-DQA101:02-DQB106:02 haplotype protects autoantibody-positive relatives from type 1 diabetes throughout the stages of disease progression. / Pugliese, Alberto; Boulware, David; Yu, Liping; Babu, Sunanda; Steck, Andrea K.; Becker, Dorothy; Rodriguez, Henry; Di Meglio, Linda; Evans-Molina, Carmella; Harrison, Leonard C.; Schatz, Desmond; Palmer, Jerry P.; Greenbaum, Carla; Eisenbarth, George S.; Sosenko, Jay M.

In: Diabetes, Vol. 65, No. 4, 01.04.2016, p. 1109-1119.

Research output: Contribution to journalArticle

Pugliese, A, Boulware, D, Yu, L, Babu, S, Steck, AK, Becker, D, Rodriguez, H, Di Meglio, L, Evans-Molina, C, Harrison, LC, Schatz, D, Palmer, JP, Greenbaum, C, Eisenbarth, GS & Sosenko, JM 2016, 'HLA-DRB115: 01-DQA101:02-DQB106:02 haplotype protects autoantibody-positive relatives from type 1 diabetes throughout the stages of disease progression', Diabetes, vol. 65, no. 4, pp. 1109-1119. https://doi.org/10.2337/db15-1105
Pugliese, Alberto ; Boulware, David ; Yu, Liping ; Babu, Sunanda ; Steck, Andrea K. ; Becker, Dorothy ; Rodriguez, Henry ; Di Meglio, Linda ; Evans-Molina, Carmella ; Harrison, Leonard C. ; Schatz, Desmond ; Palmer, Jerry P. ; Greenbaum, Carla ; Eisenbarth, George S. ; Sosenko, Jay M. / HLA-DRB115 : 01-DQA101:02-DQB106:02 haplotype protects autoantibody-positive relatives from type 1 diabetes throughout the stages of disease progression. In: Diabetes. 2016 ; Vol. 65, No. 4. pp. 1109-1119.
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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.",
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AU - Babu, Sunanda

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AU - Becker, Dorothy

AU - Rodriguez, Henry

AU - Di Meglio, Linda

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AU - Harrison, Leonard C.

AU - Schatz, Desmond

AU - Palmer, Jerry P.

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