Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays

Background Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen -2 (IA -2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to de fi ne threshold levels for diagnostic speci fi city and sensitivity. Methods IAA, GADA, IA -2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor ' s of fi ce controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1 - 10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10 -fold cross -validations to separate patients from controls either by maximizing the x 2 -statistics (chisq) or using the 98th percentile of speci fi city (Spec98). Mean and 95% CI for threshold, sensitivity and speci fi city are presented. Findings The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) speci fi city in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) speci fi city in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) speci fi city compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) speci fi city in the RBA. The diagnostic sensitivity and speci fi city were higher in PBC compared to DOC and BDC. Interpretation ADAP was comparable in two laboratories, both comparable to or better than RBA, to de fi ne threshold levels for two or more autoantibodies to stage type 1 diabetes. Funding Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co - fi nanced by EU Interreg & Ouml;KS, Capital Region of Denmark, Region Sk & aring;ne and the Novo Nordisk Foundation. Copyright (c) 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).