159-LB: High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve the Risk Prediction for Type 1 Diabetes

Abstract

Background: A cohort of children with single ZnT8 autoantibody (ZnT8A) positivity were identified in two large clinical trials, Autoimmunity Screening for Kids (ASK) and Diabetes Autoimmunity Study in the Young (DAISY), and their risk of type 1 diabetes (T1D) have never been studied. Methods: Three cohorts were analyzed using a high-affinity electrochemiluminescence (ECL) ZnT8A assay including 302 new onset T1D patients, 135 children positive for ZnT8A by standard radio-binding assay (RBA) from 23400 children screened in ASK study, and 123 children with multiple autoantibodies or single ZnT8A by RBA from 2547 children in DAISY study. Results: ECL-ZnT8A had a similar sensitivity with RBA-ZnT8A in the cohort of 302 new onset T1D patients (62.3% vs. 61.9%). In ASK, 135/23400 of general population children were positive for RBA-ZnT8A and 64/135 were found as single ZnT8A only without other islet autoantibodies. Of 64 children with single ZnT8A, only 14.1% (9/64) were detectable by ECL-ZnT8A. Antibody-affinity analysis revealed that the ZnT8A in RBA but not confirmed by ECL were of low affinity and they were easily disappeared during the follow-up behaving as ‘transient’ positivity. In terms of T1D classification from stage 1 to stage 3, positive predictive value (PPV) of ECL-ZnT8A (61/70 [87.1%]) was significantly higher than that of RBA-ZnT8A (73/137 [53.3%]; P Conclusions: Large proportion of ZnT8A by current standard RBA are single ZnT8A with majority at low risk in population-based screening while ECL-ZnT8A can discriminate high risk from low risk and are highly predictive for T1D development. Disclosure X. Jia: None. L. He: None. D. Miao: None. K. Waugh: None. C. Geno rasmussen: None. F. Dong: None. M. Rewers: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; RTI, Research Support; Self; Janssen Research & Development, LLC, JDRF. L. Yu: None. Funding Diabetes Research Center (P30DK116073); JDRF (2-SRA-2018-533-S-B, 2-SRA-2020-965-S-B, 1-SRA-2016-208-S-B); National Institutes of Health (DK32083)