Next-generation immunoassays for autoantibody detection in celiac disease: emerging technologies and diagnostic advances

The appearance of disease‑specific autoantibodies (Aab) is a hallmark of celiac disease (CeD). The recent adaption of a no‑biopsy approach places greater reliance on Aab testing. Despite their widespread use, conventional assay formats such as enzyme-linked immunosorbent assays (ELISA) continue to exhibit inherent methodological deficiencies that cannot be readily mitigated. Radio-binding assays (RBA) have historically defined the benchmark for assay performance, but the requirement for radiolabeled reagents and dedicated facilities renders this strategy an untenable solution beyond a limited number of specialized laboratories. This review aims to outline the future role of Aab in the diagnostic algorithm of CeD and to highlight the next-generation techniques that could replace the conventional testing methods. We discuss the diagnostic utility of ELISA, RBA, Electrochemiluminescence assay (ECL), luciferase immunoprecipitation systems (LIPS), antibody detection by agglutination polymerase chain reaction (ADAP) and dissociation enhanced lanthanide fluorescence immunoassay (DELFIA) techniques with emphasis on measuring anti-Transglutaminase 2 (TG2) Aab in the diagnosis of CeD. With the advantages of automation and multiplexing, the new generation of Aab testing modalities like ECL and ADAP may demonstrate sufficient sensitivity and accuracy to warrant inclusion in future CeD diagnostic guidelines. While multiplexing allows the inclusion of multiple Aabs testing from small volumes of blood in an automated manner, this generation of immunoassays are well suited for large-scale screenings and may replace the conventional ELISA and RBA techniques in the near future.