ArticleThe Journal of clinical endocrinology and metabolism2022
Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA Haplotypes.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The trial behind it
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Trial
- Genetic association stratified by HLA-DR3 and HLA-DR4 status reveals heterogeneity in pathways of progression to type 1 diabetes.Diabetologia · 2026Article
- Polygenic score from MODY genes is associated with type 1 diabetes and disease characteristics.Acta diabetologica · 2025Article
- Characteristics of autoantibody-positive individuals without high-risk HLA-DR4-DQ8 or HLA-DR3-DQ2 haplotypes.Diabetologia · 2025Article
- Next-generation sequencing reveals additional HLA class I and class II alleles associated with type 1 diabetes and age at onset.Frontiers in immunology · 2024Article
- Clinical and HLA genotype analysis of immune checkpoint inhibitor-associated diabetes mellitus: a single-center case series from China.Frontiers in immunology · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveElectrochemiluminescence (ECL) assays are high-affinity autoantibody (Ab) tests that are more specific than Abs detected by traditional radiobinding assays (RBA) for risk screening and prediction of progression to type 1 diabetes. We sought to characterize the association of high-risk human leukocyte antigen (HLA) haplotypes and genotypes with ECL positivity and levels in relatives of individuals with type 1 diabetes.
methodsWe analyzed 602 participants from the TrialNet Pathway to Prevention Study who were positive for at least 1 RBA diabetes-related Ab [glutamic acid decarboxylase autoantibodies (GADA) or insulin autoantibodies (IAA)] and for whom ECL and HLA data were available. ECL and RBA Ab levels were converted to SD units away from mean (z-scores) for analyses.
resultsMean age at initial visit was 19.4 ± 13.7 years; 344 (57.1%) were female and 104 (17.3%) carried the high-risk HLA-DR3/4*0302 genotype. At initial visit 424/602 (70.4%) participants were positive for either ECL-GADA or ECL-IAA, and 178/602 (29.6%) were ECL negative. ECL and RBA-GADA positivity were associated with both HLA-DR3 and DR4 haplotypes (all Ps < 0.05), while ECL and RBA-GADA z-score titers were higher in participants with HLA-DR3 haplotypes only (both Ps < 0.001). ECL-IAA (but not RBA-IAA) positivity was associated with the HLA-DR4 haplotype (P < 0.05).
conclusionsECL-GADA positivity is associated with the HLA-DR3 and HLA-DR4 haplotypes and levels are associated with the HLA-DR3 haplotype. ECL-IAA positivity is associated with HLA-DR4 haplotype. These studies further contribute to the understanding of genetic risk and islet autoimmunity endotypes in type 1 diabetes.
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