General population screening of T1D in children using electrochemiluminescence (ECL) multiplex assay

The Autoimmunity Screening for Kids (ASK) program is design to determine the prevalence of pre-symptomatic type 1 diabetes (T1D) and celiac disease (CD) in Denver general population children 1-17 y old. In the initial 16 months, 8120 children were screened for GADA, IA-2A, mIAA as well as for transglutaminase autoantibody (TGA) using both standard radio-binding assay (RBA) and a multiplex electrochemiluminescence (ECL) assay; ZnT8A was measured by RBA only. Positive children are re-tested 2-6 weeks later. At the initial screening, 3.41% (277/8120) of children were positive for at least one islet autoantibody (iAb) by RBA and an additional 26 children (0.32%) were positive for iAb by ECL only. Multiple iAb at screening or confirmation were present in 0.79% of non-Hispanic whites (NHW) and in 0.33% of the other children. ECL assay was congruent with RBA in 91% and identified three additional multiple iAb cases. A single iAb was detected by both RBA and ECL in 0.63% of NHW and 0.55% of the other children. Of the 236 children with a single RBA iAb, 79% were not confirmed by ECL assay. These RBA iAbs were usually at lower levels and have been previously shown to be of low-affinity and not predictive of progression to multiple iAb and T1D ASK is following all iAb positive children to prevent DKA at diagnosis and enroll those eligible into prevention trials. In conclusion, ASK indicates that 85% of the general population children found to be iAb positive by the current ‘gold standard’ RBAs express a single iAb and 79% of those are not at increased risk for T1D. There are ethnic differences in the prevalence of pre-symptomatic stage 1 T1D. Future general population screening programs should consider a two-step approach with highly sensitive initial screening followed by conformation focused on multiplex or single high-affinity autoantibodies.