期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 4, 页码 E1510-E1517出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab853
关键词
type 1 diabetes; epidemiology; electrochemiluminescence assay; prediction; genetics; HLA genotyping; autoantibody
资金
- NIDDK K12 training grant [K12DK094712]
- Type 1 Diabetes TrialNet Pathway to Prevention Study Group [NCT00097292]
- National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK103180, U01-DK103153, U01-DK085476, U01-DK103266]
- Juvenile Diabetes Research Foundation International (JDRF)
Objective Electrochemiluminescence (ECL) assays are high-affinity autoantibody tests used for risk screening and prediction of type 1 diabetes progression. This study analyzed the association of high-risk HLA haplotypes and genotypes with ECL positivity in relatives of individuals with type 1 diabetes, showing that ECL-GADA and ECL-IAA positivity are associated with HLA-DR3 and HLA-DR4 haplotypes, respectively.
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.
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