Introduction and Objective: In general population screening for type 1 diabetes (T1D), large proportion of islet autoantibodies (IAbs) detected by the standard radio-binding assay (RBA) are not predictive due to low-affinity. Electrochemiluminescence (ECL) IAb assay has been shown in multiple studies to improve predictive accuracy by detecting high-affinity IAbs. Our new bridging ELISA for insulin autoantibodies (IAA) is designed with a similar assay mechanism of ECL assay. This study aims to assess the new ELISA-IAA assay for T1D prediction compared to RBA and ECL in the Autoimmunity Screening for Kids (ASK) study, a general population T1D screening study.Methods: Serum samples from 138 randomly selected new onset T1D patients (within two weeks) positive for RBA-IAA and 327 control samples negative for all IAbs were tested to validate the new ELISA IAA assay. ELISA-IAA was then performed on 202 children from the ASK study positive for RBA-IAA: 71 with multiple IAbs, and 131 with IAA only including 52 positivity by both RBA and ECL and 79 only by RBA.Results: With the specificity set at the 99.4th percentile of 327 control subjects, the bridging ELISA detected IAA in 136 (98.6%) of 138 newly diagnosed T1D patients. Among ASK participants with multiple IAbs, 80.3% (57/71) were ELISA-IAA positive (of 14 negative by ELISA, 7 were negative by ECL-IAA). In contrast, only 48.1% (63/131) were ELISA-IAA positive overall in children with single IAA alone (p<0.0001). Among single IAA, ELISA-IAA positivity was 78.9% (41/52) in those positive for ECL-IAA and only 27.9% (22/79, p<0.0001) in those negative for ECL-IAA.Conclusion: With the comparable sensitivity and specificity to RBA in new-onset T1D patients vs. controls, the new bridging ELISA identifies high-risk IAA significantly among those with multiple IAbs and the high-affinity single IAA by ECL assay. This ELISA-IAA assay will be a practical tool with a high predictive value and easy to use across the laboratories for both population-based screening and clinical diagnosis.
C. Zhang: None. K. Waugh: None. A.W. Michels: Stock/Shareholder; IM Therapeutics. Advisory Panel; Sanofi. M. Rewers: Consultant; Sanofi. Research Support; Sanofi. L. Yu: None. X. Jia: None.
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