{"doi":"10.1210/clinem/dgab853","title":"Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA Haplotypes","abstract":"OBJECTIVE: Electrochemiluminescence (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. METHODS: We 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. RESULTS: Mean 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). CONCLUSIONS: ECL-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.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":194408,"datarank":0.6298730524898994,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.2701887615701437,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.2701887615701437,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":8,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00097292"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254435,"name":"Laura Pyle","orcid":"0000-0001-5577-8221","position":1,"is_corresponding":false},{"id":764242,"name":"Hali Broncucia","orcid":"0000-0003-2056-2169","position":2,"is_corresponding":false},{"id":502919,"name":"Taylor Armstrong","orcid":"0000-0003-4931-2331","position":3,"is_corresponding":false},{"id":39947,"name":"Liping Yu","orcid":"0000-0003-0664-2154","position":4,"is_corresponding":false},{"id":336608,"name":"Peter A. Gottlieb","orcid":"0000-0002-7601-8536","position":5,"is_corresponding":false},{"id":96015,"name":"Andrea K. Steck","orcid":"0000-0002-5931-9484","position":6,"is_corresponding":false},{"id":533259,"name":"Taylor M. Triolo","orcid":"0000-0003-4796-6542","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-18T23:49:59.476757Z","pmid":"34850014","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}