ArticleDiabetologia2008
Autoantibodies to islet antigen-2 are associated with HLA-DRB1*07 and DRB1*09 haplotypes as well as DRB1*04 at onset of type 1 diabetes: the possible role of HLA-DQA in autoimmunity to IA-2.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 34 citations in OpenAlex.
- Anti-GAD antibody-negative, anti-IA2 antibody-positive slowly progressive insulin-dependent diabetes mellitus and Graves' disease preceded by childhood-onset minimal change nephrotic syndrome: a case report.Diabetology international · 2025Article
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- Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation inRNA (New York, N.Y.) · 2017Article
- Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes.Diabetologia · 2016Article
- Non-HLA type 1 diabetes genes modulate disease risk together with HLA-DQ and islet autoantibodies.Genes and immunity · 2015Article
- Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation.BMC medical genomics · 2014Article
- Genetics: new HLA variants could predict T1DM risk in African Americans.Nature reviews. Endocrinology · 2013Article
- HLA class II genotyping of African American type 1 diabetic patients reveals associations unique to African haplotypes.Diabetes · 2013Article
- Recursive organizer (ROR): an analytic framework for sequence-based association analysis.Human genetics · 2013Article
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- HLA-associated phenotypes in youth with autoimmune diabetes.Pediatric diabetes · 2013Article
- Autoantibodies and high-risk HLA susceptibility markers in first-degree relatives of Brazilian patients with type 1 diabetes mellitus: a progression to disease based study.Journal of clinical immunology · 2012Article
- Rising incidence of type 1 diabetes is associated with altered immunophenotype at diagnosis.Diabetes · 2012Article
- GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA).Drugs of the future · 2011Article
- Evidence that HLA class I and II associations with type 1 diabetes, autoantibodies to GAD and autoantibodies to IA-2, are distinct.Diabetes · 2011Article
- Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.PLoS genetics · 2011Article
- Predictors of associated autoimmune diseases in families with type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium.Diabetes/metabolism research and reviews · 2011Article
- Article
- Humoral autoimmunity against the extracellular domain of the neuroendocrine autoantigen IA-2 heightens the risk of type 1 diabetes.Endocrinology · 2010Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisTo further our understanding of antigen presentation by HLA class II molecules, we have examined the influence of HLA class II genotype on expression of autoantibodies to islet antigen-2 (IA-2A).
methodsHLA class II genotype and IA-2A were determined within 3 months of diagnosis in 618 patients with type 1 diabetes (median age 11 years [range 0.7-20.9]). Antibodies to the juxtamembrane region of IA-2 were measured by a radiobinding assay in 481 of 484 IA-2A-positive patients.
resultsIA-2A prevalence was highest in patients carrying at least one HLA-DRB1*04-DQA1*0301 (385 of 450; 86%), DRB1*07-DQA1*(0201 or 0301) (58 of 64; 91%) or DRB1*09-DQA1*0301 haplotype (18 of 19; 95%). Multiple regression showed that IA-2A were strongly associated with the number of these haplotypes carried; only 69 of 132 (52%) patients carrying none of these haplotypes had IA-2A, compared with 322 of 391 (82%) patients with one and 93 of 95 (98%) with two of these haplotypes (p < 0.001). IA-2 juxtamembrane antibodies were less frequent in IA-2A-positive patients with one (35%) or two (36%) DRB1*03-DQB1*02 or DRB1*07-DQB1*02 haplotypes than in those negative for these haplotypes (52%) (p = 0.002), but showed an independent positive association with IA-2A level (p < 0.001). CONCLUSIONS/
interpretationHLA class II alleles strongly influence the prevalence of IA-2A. The high IA-2A prevalence in patients carrying DRB1*04, DRB1*07 and DRB1*09 alleles in linkage disequilibrium with DQA1*0301 or the closely related DQA1*0201 suggests the humoral response to IA-2 may be driven by HLA-DQA1 genes.
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