Comparative Analysis of the Sensitivity, Specificity, Concordance, and 5-Year Predictive Power of Diabetes-Related Autoantibody Assays

by sugaradmin



This study compares novel type 1 diabetes–related autoantibody assays developed to improve upon the standard radiobinding assay (RBA). Samples from 1,505 individuals, followed for 5 years or to clinical type 1 diabetes, originally tested by RBA were aliquoted and sent blindly to five laboratories (Barbara Davis Diabetes Center [BDC], Institute of Diabetes Research [IDR], Diabetes Research Institute [DRI], Meso Scale Discovery [MSD], and Enable Biosciences) to be tested by electrochemiluminescence (ECL) assays, Luciferase Immuno Precipitation System (LIPS) assays, multiplex antibody detection by agglutination-PCR (ADAP) assays, and N-terminally truncated GAD65 or IA2β autoantibody RBAs (tGADA/IA2βA). The fraction of samples that were concordant for negative/positive interpretations across all assays were 79.7% (GADA), 65.2% (tyrosine phosphatase-related insulinoma antigen 2 [IA-2A]), 36.2% (insulin autoantibodies [IAA]), and 67.5% (zinc transporter 8 [ZnT8A]). The assays with the highest Youden J index for predicting the previous RBA results differed by autoantibody: 0.65 LIPS (IDR) for IAA, 0.91 ECL (BDC) for ZnT8A, 0.82 tGADA RBA (IDR) for GADA, 0.91 ECL (MSD and BDC) for IA-2A. The Youden J index for predicting 5-year type 1 diabetes varied significantly across assays and was highest for LIPS (DRI) for all autoantibody combinations, with little variation in the respective maximum Youden J index. The discordance between assays makes it problematic to interpret positivity when comparing results from different assays. Longitudinal autoantibody assessments should be tested with the same assay.

ARTICLE HIGHLIGHTS
  • Interassay concordance and 5-year diabetes prediction of islet cell autoantibody detection using the radiobinding assay (TrialNet), two independently developed multiplex electrochemiluminescence detection methods, the luciferase immune precipitation system, detection by agglutination-PCR, and truncated GADA, and IA2βA radiobinding assays are reported.
  • There was considerable discordance that varied by type of autoantibody across the assays.
  • Type 1 diabetes prediction was relatively high and uniform, implying confirmation of increased diabetes risk among those who are multiple autoantibody positive, although substantial false positive rates need to be considered when autoantibodies alone are used for screening to identify high diabetes risk.





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