A low-volume rapid luciferase immunoprecipitation system (LIPS) assay utilising a novel antigen to detect autoantibodies to zinc transporter 8 (ZnT8A) in type 1 diabetes provides an alternative to conventional radioimmunoassay

Claire L Williams, Kathleen M Gillespie, V Lampasona, Alistair J K Williams, Anna E Long*

*Corresponding author for this work

Research output: Contribution to conferenceConference Abstractpeer-review

Abstract

Aims: Present in ~70% of new-onset diabetes cases, autoantibodies to zinc transporter 8 (ZnT8A) are one of the four major markers of islet autoimmunity used to identify high-risk individuals. We sought to compare the performance of a novel luciferase-based ZnT8 immunoassay (Nluc-ZnT8) with the “gold standard” radioimmunoassay. Method: The Nluc-ZnT8 was evaluated using samples previously tested by ZnT8A radioimmunoassay from 589 new-onset diabetes [sampled within 3 months of diagnosis; 329 males; median diagnosis age 11 years (range 1-55)] and 300 relatives who progressed to diabetes [median follow-up 12.4 years (range 0.2-31); 127 males; median age at sample 28 years (range 1.4-64.1]. Positivity thresholds were set at the 97.5th percentile of 523 healthy schoolchildren (range 9.0-14years). Units were derived from a logarithmic standard curve. Results: Levels of autoantibodies detected by Nluc-ZnT8 and radioimmunoassay were highly correlated [Spearman’s R= 0.90; p<0.0001]. In ZnT8A radioimmunoassay positives, 379/402 (94.3%) were Nluc-ZnT8 positive. Of 187 radioimmunoassay negatives, an additional 31 (17%) new-onset diabetes were identified by Nluc-ZnT8. The majority of discrepant samples (80%) had low level ZnT8A (<3 units) and therefore, may be explained by detection limits and assay format. In relatives positive by both assays, the 20-year diabetes risk was 58%. Of 60 ZnT8A radioimmunoassay positive relatives and, 240 radioimmunoassay negative relatives, 54 (90%) and 30 (13%) were positive respectively, by Nluc-ZnT8. Conclusion: This Nluc-ZnT8 LIPs assay provides a cheaper, higher throughput, lower serum volume alternative to radioimmunoassay that can discriminate diabetes risk and therefore, should facilitate large-scale screening for type 1 diabetes risk.
Original languageEnglish
Publication statusPublished - 19 Apr 2021
EventDiabetes UK Professional Conference 2021 - Online
Duration: 16 Apr 202130 Apr 2021
https://www.diabetes.org.uk/diabetes-uk-professional-conference

Conference

ConferenceDiabetes UK Professional Conference 2021
Period16/04/2130/04/21
Internet address

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