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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
- 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.
- Subjects :
- Adult
Male
musculoskeletal diseases
0301 basic medicine
Adolescent
endocrine system diseases
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Human leukocyte antigen
Biology
HLA-DQ alpha-Chains
Diabetes Complications
Young Adult
03 medical and health sciences
0302 clinical medicine
Risk Factors
immune system diseases
Diabetes mellitus
Internal Medicine
medicine
HLA-DQ beta-Chains
Humans
Family
Genetic Predisposition to Disease
Cumulative incidence
Allele
skin and connective tissue diseases
Child
HLA-DRB1
Autoantibodies
Type 1 diabetes
Haplotype
Autoantibody
nutritional and metabolic diseases
Genetics/Genomes/Proteomics/Metabolomics
medicine.disease
Diabetes Mellitus, Type 1
030104 developmental biology
Haplotypes
Child, Preschool
Immunology
Disease Progression
Female
HLA-DRB1 Chains
Subjects
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