Interlaboratory Evaluation of Multiplex Autoantibody Assay Performance in the Islet Autoantibody Standardization...

Area of Science:

• Endocrinology
• Immunology
• Clinical Diagnostics

Background:

• Type 1 diabetes is diagnosed by detecting islet autoantibodies.
• Multiplex assays simultaneously measure multiple autoantibodies, aiding population screening.
• The Islet Autoantibody Standardization Program (IASP) facilitates assay evaluation.

Purpose of the Study:

• To report 2024 IASP workshop results for multiplex islet autoantibody assays.
• To assess the performance of various multiplex assay platforms in detecting type 1 diabetes autoantibodies.
• To identify areas for standardization in multiplex assay use for screening programs.

Main Methods:

• Fifteen laboratories analyzed coded sera from type 1 diabetes patients and controls using 19 multiplex assays.
• Assays included antibody-dependent agglutination PCR (ADAP), bridge-ELISA, electrochemiluminescence, and luciferase immunoprecipitation system (LIPS).
• Performance metrics included sensitivity, specificity, ROC-AUC, and partial ROC-AUC at 95% specificity (pAUC95).

Main Results:

• Median ROC-AUC was 0.98, indicating good overall assay performance.
• Adjusted sensitivity at 99% specificity ranged from 93-97%, effectively reducing false positives.
• Bridge-ELISA platforms showed potential for universal cutoff standardization, while ADAP exhibited significant interlaboratory threshold variation.

Conclusions:

• Multiplex assays demonstrate strong performance in detecting islet autoantibodies and differentiating type 1 diabetes cases from controls.
• Interlaboratory variability and platform-specific differences highlight the need for continued standardization efforts.
• Sequential testing strategies may be required to achieve the high specificity needed for population screening.