ArticleDiabetes2011
Evidence that HLA class I and II associations with type 1 diabetes, autoantibodies to GAD and autoantibodies to IA-2, are distinct.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents.Pediatric diabetes · 2018Guideline
- (2) Classification and diagnosis of diabetes.Diabetes care · 2015Guideline
- IA-2A positivity increases risk of progression within and across established stages of type 1 diabetes.Diabetologia · 2025Article
- Immune-evasive beta cells in type 1 diabetes: innovations in genetic engineering, biomaterials, and computational modeling.Frontiers in immunology · 2025Review
- An Adult Case of Diabetes With High Levels of GAD Antibodies Without Insulin Deficiency for More Than 10 Years.Case reports in endocrinology · 2025Article
- Association of C1QTNF6 gene polymorphism with risk and clinical features of type 1 diabetes in Chinese: implications for ZnT8A and beta-cell function.Frontiers in immunology · 2025Article
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Antigen-specific T cell responses in autoimmune diabetes.Frontiers in immunology · 2024Review
- Relative Frequency of Islet Autoimmunity in Children and Adolescents with Autoimmune Thyroid DiseaseJournal of clinical research in pediatric endocrinology · 2023Article
- HLA-DR3 mediated CD4 T cell response against GAD65 in type 1 diabetes patients.Journal of diabetes · 2023Article
- The longitudinal loss of islet autoantibody responses from diagnosis of type 1 diabetes occurs progressively over follow-up and is determined by low autoantibody titres, early-onset, and genetic variants.Clinical and experimental immunology · 2022Article
- Article
- HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes.Diabetologia · 2021Article
- HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.Transplantation direct · 2021Article
- Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients.Journal of diabetes research · 2021Article
- Primary DQ effect in the association between HLA and neurological syndromes with anti-GAD65 antibodies.Journal of neurology · 2020Article
- Circulating β cell-specific CD8Clinical and experimental immunology · 2020Article
- Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC.Diabetes care · 2020Article
- Distinct HLA Associations with Rheumatoid Arthritis Subsets Defined by Serological Subphenotype.American journal of human genetics · 2019Article
- Immunoglobulin M gene association with autoantibody reactivity and type 1 diabetes.Immunogenetics · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveA major feature of type 1 diabetes is the appearance of islet autoantibodies before diagnosis. However, although the genetics of type 1 diabetes is advanced, the genetics of islet autoantibodies needs further investigation. The primary susceptibility loci in type 1 diabetes, the HLA class I and II genes, are believed to determine the specificity and magnitude of the autoimmune response to islet antigens. We investigated the association of glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen-2 autoantibodies (IA-2A) with the HLA region. RESEARCH DESIGN AND
methodsAssociations of GADA and IA-2A with HLA-DRB1, HLA-DQB1, HLA-B, HLA-C, HLA-A, MICA, and 3,779 single nucleotide polymorphisms (SNPs) were analyzed in 2,531 childhood-onset case subjects (median time since diagnosis 5 years). All analyses were adjusted for age-at-diagnosis and duration of diabetes.
resultsGADA and IA-2A were associated with an older age-at-diagnosis (P < 10(-19)). For GADA, the primary association was with HLA-DQB1 (P = 9.00 × 10(-18)), with evidence of a second independent effect in the HLA class I region with SNP, rs9266722 (P = 2.84 × 10(-6)). HLA-DRB1 had the strongest association with IA-2A (P = 1.94 × 10(-41)), with HLA-A*24 adding to the association, albeit negatively (P = 1.21 × 10(-10)). There was no evidence of association of either IA-2A or GADA with the highly type 1 diabetes predisposing genotype, HLA-DRB1*03/04.
conclusionsDespite genetic association of type 1 diabetes and the islet autoantibodies localizing to the same HLA class II genes, HLA-DRB1 and HLA-DQB1, the effects of the class II alleles and genotypes involved are quite different. Therefore, the presence of autoantibodies is unlikely to be causal, and their role in pathogenesis remains to be established.
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