1315-P: Application of Multiplex ECL Assay in Mass Screening for Presymptomatic Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: JIA, XIAOFAN, HE, LING, MIAO, DONGMEI, WAUGH, KATHLEEN, FROHNERT, BRIGITTE I., STECK, ANDREA, REWERS, MARIAN, YU, LIPING, GENO RASMUSSEN, CRISTY R.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2020
• Subjects: Affinity; Autoantibodies; Autoimmunity; Children; Diabetes; Diabetes mellitus (insulin dependent); Glutamate decarboxylase; Insulin; Pediatrics
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-1315-P

Islet autoantibody (IAb) assays for a general population screening should ideally be high-troughput, low-cost, and offer high-sensitivity and high positive predictive value in a low-risk population. The Autoimmunity Screening for Kids (ASK) study has compared the performance of the ’gold standard’ radiobinding assays (RBAs) and a multiplex electrochemiluminesence assay (ECL) in a large unselected pediatric population. Single IAb by RBA but negative by ECL have been previously shown to be low-affinity and of low predictive value for progression to clinical diabetes. From 2017-2019, ASK screened for IAbs 23,400 Colorado children ages 1-17 y. A high-throughput multiplex ECL assay combining IAbs to insulin, GAD and IA-2 in one single well was used in parallel with standard non-multiplex RBAs. At the initial screening with RBA, 3.0% (697/23400) of children were positive for at least one IAb, including 0.4% (98/23400) for multiple IAbs and 2.6% (599/23400) for a single IAb. Among children with ≥2 IAbs, ECL assay results were 89.8% congruent with RBA. In contrast, only 21.5% (129/599 p<0.0001) of children with single IAb by RBA were ECL positive (i.e., high-affinity). During a median follow-up of 0.5 y (range 0.1-2.5 y), 90% (98/109) of children with a single IAb by both RBA and ECL remained persistently positive and 9.2% of those progressed to ≥2 IAbs. In contrast, 74% (242/328, p=0.0003) of children with a single IAb by RBA but ECL negative remained persistently positive; only 1.8% (p=0.001) of those converted to ≥2 IAbs (half became ECL positive). ASK results suggest that applying the ECL assay as the confirmation test may help to remove nearly 80% of subjects with single IAb from further follow-up and monitoring, with little loss of sensitivity. Alternatively, the multiplex ECL could be used as the primary screening tool to leverage its high throughput and low cost, compared to RBAs.