An ECL-based Autoantibody Assay for Early Diagnosis of T1D Using a Membrane-spanning ZnT8 Antigenic Domain

Unmet Need
Approximately 1.25 million people in the US have type 1 diabetes (T1D) and the rates of newly diagnosed cases in children are on the rise each year. T1D is caused by the development of an autoimmune reaction to pancreatic β cells. The first detectable sign of β cell autoimmunity is the appearance of diabetes-associated autoantibodies, which include antibodies to insulin, islet antigen 2, and zinc transporter 8 (ZnT8). However, current assays to measure autoantibodies to ZnT8 are only able to measure antibodies to the C terminal domain (CTD), not the transmembrane domain (TMD). This is a major limitation because the CTD region is significantly smaller than the TMD region and the use of this assay will not identify all the autoantibodies to the extracellular domain of ZnT8. Consequently, an assay to detect autoantibodies to the native extracellular domain of ZnT8 would potentially improve our understanding of the mechanisms of T1D progression and be a useful diagnostic tool.
 
Technology Overview
Johns Hopkins and University of Colorado, Denver, researchers developed an assay to detect autoantibodies to the extracellular domain of ZnT8, including the TMD region. This assay stabilizes the extracellular domain’s native structure, by using an antibody that complexes with the intracellular domain of ZnT8. This assay is electrochemiluminescence based and is able to identify serum that is positive for autoantibodies to ZnT8ec. The inventors found that 21% of T1D plasma sampled in a cohort of 130 samples was positive for antibodies to ZnT8ec.This assay might also prove useful as a diagnostic for T1D, and may aid in the identification of patients at risk of T1D earlier.
 
Stage of Development
Researchers have developed an assay to detect autoantibodies to the extracellular domain of ZnT8.
 
Publications
Gu, Y, et al., Diabetes 68, 2019.
 
 

Category(s):