Performance assessment of a novel fully automated ELISA for anti-IA2 autoantibody detection in type 1 diabetes.

Autoantibodies to insulinoma-associated antigen 2 (IA2) are well-established biomarkers of islet autoimmunity, supporting the diagnosis and risk stratification of type 1 diabetes (T1D). This study presents the analytical and clinical evaluation of a newly developed bridge-type Anti-IA2 ELISA (Euroimmun), which is CE-marked under the European In Vitro Diagnostic Regulation (IVDR) and compatible with fully automated processing platforms. The analytical performance was assessed through precision, detection capability, linearity, and interference studies. Diagnostic accuracy testing and method comparison with the predecessor ELISA and the Medipan CentAK anti-IA2 M radioimmunoassay were performed using serum samples from patients with T1D (median age at diagnosis: 11 years; median diabetes duration: 4 years), latent autoimmune diabetes in adults, or Addison's disease, as well as samples from non-T1D control groups and the Islet Autoantibody Standardization Program (IASP). The assay demonstrated low intra-/inter-lot imprecision (CVs ≤ 3.2%), detection limits in the low IU/mL range, linearity over the measuring range (10-2000 IU/mL), and no interference from hemolytic, lipemic, or icteric sample conditions. Sensitivity was 53.8% in the clinical T1D cohort (56.5% in newly diagnosed patients), and 76.0% in IASP case samples. Specificity in non-T1D controls reached 98.4%. Agreement with the predecessor ELISA was almost perfect (94.7%; κ = 0.873). Compared with the radioimmunoassay, substantial agreement (82.4-83.8%; κ ≥ 0.637) was observed, and the ELISA identified more anti-IA2-positive T1D samples. In conclusion, the new Anti-IA2 ELISA combines strong analytical and diagnostic performance with a fully automated workflow enabling standardized end-to-end processing. These features support implementation in high-throughput routine diagnostics. Prospective validation in larger and population-representative cohorts is warranted to further assess the assay's suitability for potential future use in large-scale screening aimed at improving early detection and risk assessment in autoimmune diabetes.