title: 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.
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.
authors.affiliation: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL apuglies@med.miami.edu.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: David
authors.initials: D
authors.lastname: Boulware
authors.affiliation: Division of Bioinformatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.affiliation: Division of Bioinformatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: Sunanda
authors.initials: S
authors.lastname: Babu
authors.affiliation: Division of Bioinformatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Becker
authors.affiliation: Department of Pediatrics at the Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Henry
authors.initials: H
authors.lastname: Rodriguez
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL.
authors.forename: Linda
authors.initials: L
authors.lastname: DiMeglio
authors.affiliation: Department of Pediatric Endocrinology, Riley Hospital for Children at Indiana University Health, Indianapolis, IN.
authors.forename: Carmella
authors.initials: C
authors.lastname: Evans-Molina
authors.affiliation: Department of Medicine, Indiana University School of Medicine and the Richard L. Roudebush VA Medical Center, Indianapolis, IN.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL.
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
authors.affiliation: VA Puget Sound Health Care System and University of Washington, Seattle, WA.
authors.forename: Carla
authors.initials: C
authors.lastname: Greenbaum
authors.affiliation: Division of Bioinformatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.affiliation: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL Benaroya Research Institute, Seattle, WA.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Sosenko
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D048909:Diabetes Complications / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D018450:Disease Progression; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen
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