Detection of Islet Autoantibodies in Whole Blood by Antibody Detection by Agglutination-PCR (ADAP) Technology Is Sensitive and Suitable for General Population Screening Programs

Background. Detection of type 1 diabetes (T1D) at the preclinical stage is possible by detecting islet autoantibodies (IAs) years before the appearance of symptomatic diabetes. The Antibody Detection Israeli Research is a general population screening program searching for children with multiple IAs who are at risk of developing T1D. IAs are measured in capillary or venous whole blood (WB) samples using the novel ultrasensitive antibody detection by agglutination-PCR (ADAP) technology. Objective. To assess the accuracy and reliability of the ADAP assay in venous and capillary WB. Materials and Methods. In total, 50 children with T1D and 50 healthy controls participated in the study. Venous and capillary blood samples were drawn from participants with T1D, while only venous blood was drawn from the controls. The ADAP assay in venous and capillary blood was compared to the currently used assays in their ability to detect glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), and insulin autoantibodies (IAAs). Results. The area under the curve using the receiver operating characteristic curves was comparable between the ADAP assay in WB and standard enzyme-linked immunosorbent assay (ELISA)/radioimmunoassay (RIA) for all three IAs GADA 0.946 (95% CI: 0.900-0.991) vs. 0.949 (0.906-0.992), P=0.873; IA-2A 0.747 (0.649-0.844) vs. 0.666 (0.587-0.744), P=0.106; IAA 1.000 (1.000-1.000) vs. 1.000 (1.000-1.000), P=1.000. The correlation between the levels of IA in venous and capillary WB using ADAP was R-2 = 0.958 (P <0.01), R-2 = 0.943 (P <0.01), and R-2 = 0.711 (P <0.01) for GADA, IA-2A, and IAA, respectively. IA levels in venous and capillary WB using ADAP were comparable without a proportional bias in Bland-Altman's plots of agreement, suggesting the two methods may be used interchangeably. Conclusions. The ADAP assay is reliable in detecting IA in venous and capillary WB samples with comparable performance to standard RIA and ELISA. These findings open avenues for widespread use of the ADAP assay in future general population screening programs to detect children at risk of developing T1D.