Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA Haplotypes

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 leukocyt...

Full description

Saved in:
Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2022-03, Vol.107 (4), p.e1510-e1517
Main Authors: Triolo, Taylor M, Pyle, Laura, Broncucia, Hali, Armstrong, Taylor, Yu, Liping, Gottlieb, Peter A, Steck, Andrea K
Format: Article
Language:English
Subjects:
Adolescent
Adult
Autoantibodies
Autoimmunity
Child
Child, Preschool
Development and progression
Diabetes Mellitus, Type 1 - diagnosis
Epidemiology
Female
Genetic aspects
Glutamate
Glutamate Decarboxylase
Haplotypes
Histocompatibility antigens
HLA Antigens - genetics
HLA histocompatibility antigens
HLA-DR3 Antigen - genetics
HLA-DR4 Antigen - genetics
Humans
Insulin Antibodies
Male
Online Only
Risk factors
Type 1 diabetes
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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). 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.
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgab853