High-throughput multiplexed autoantibody detection to screen type 1 diabetes and multiple autoimmune diseases simultaneously

Yong Gu,Zhiyuan Zhao,Kathleen C. Waugh,D. Miao,Xiaofan Jia,Jeremy Cheng,A. Michels,M. Rewers,Tao Yang,Liping Yu

Published 2019 in EBioMedicine

ABSTRACT

Background Islet autoantibodies (IAbs) are the most reliable biomarkers to assess risk of progression to clinical type 1 diabetes (T1D). There are four major biochemically defined IAbs currently used in clinical trials that are equally important for disease prediction. The current screening methods use a radio-binding assay (RBA) for single IAb measurement, which are laborious and inefficient for large-scale screening. More importantly, up to 40% of patients with T1D have other autoimmune conditions that can be identified through relevant autoantibody testing. Thus, there is a need to screen for T1D and other autoimmune diseases simultaneously. Methods Based on our well-established electrochemiluminescence (ECL) assay platform, we developed a multiplexed ECL assay that combines 7 individual autoantibody assays together in one single well to simultaneously screen T1D, and three other autoimmune diseases including celiac disease, autoimmune thyroid disease and autoimmune poly-glandular syndrome-1 (APS-1). The 7-Plex ECL assay was extensively validated against single antibody measurements including a standard RBA and single ECL assay. Findings The 7-Plex ECL assay was well correlated to each single ECL autoantibody assay and each RBA. Interpretation The multiplexed ECL assay provides high sensitivity and disease specificity, along with high throughput and a low cost for large-scale screenings of T1D and other relevant autoimmune diseases in the general population. Fund JDRF grants 2-SRA-2015-51-Q-R, 2-SRA-2018-533-S-B, NIH grants DK32083 and DK32493. NSFC grants 81770777.

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