Evaluation of IgA deficiency using chemiluminescence immunoassays in patients with suspected celiac disease

Celiac disease (CD) is a systemic immune-mediated disorder triggered by gluten intake in genetically predisposed individuals. First-line serological screening involves measuring anti-tissue transglutaminase IgA antibodies (anti-tTG IgA) together with total IgA levels to identify IgA deficiency, in which IgA-class markers may yield negative results, leading to a false-negative diagnosis. In such cases, testing for anti-deamidated gliadin peptides IgG antibodies (anti-DGP IgG) is recommended. In this scenario, the study evaluated the ability of the anti-tTG IgA test using chemiluminescence immunoassay (ChLIA) on the automated IDS-iSYS platform (IDS-Euroimmun), to identify possible IgA deficit within a single analytical step. Furthermore, agreement with the pre-characterization results and the manufacturer’s cut-off (0.8 AU/mL) adequacy were evaluated using statistical analysis. The study analyzed 443 serological samples from patients with suspected CD, divided into three groups based on total IgA levels: NO DEFICIT (n=237), BORDERLINE (n=76), and DEFICIT (n=130). The samples were analyzed in ChLIA for anti-tTG IgA and anti-DGP IgG. Discordant results were further investigated with anti-tTG IgA and anti-DGP IgG accredited tests using enzyme-linked immunosorbent assay (ELISA) and anti-endomysial (EMA), IgA and IgG, tests using indirect immunofluorescence assay (IFA). A receiver operating characteristic (ROC) curve analysis was also performed to identify the optimal cut-off for detecting IgA deficiency. The anti-tTG IgA ChLIA test showed excellent overall agreement (98.3%) with pre-characterization. Its good analytical performance was further confirmed by comparison with the accredited ELISA method, which, in contrast, revealed a high percentage of discordant results compared to ChLIA for anti-DGP IgG. The anti-tTG IgA ChLIA test identified 223/443 samples as potentially deficient, including 26/237 NO DEFICIT samples, 71/76 BORDERLINE samples, and 126/130 DEFICIT samples. ROC analysis demonstrated excellent discriminatory power with an area under the curve (AUC) of 0.982. Youden’s index (J) identified 0.35 AU/mL as the optimal cut-off (adjusted to 0.4 AU/mL for platform’s resolution reasons), which provided better results than the manufacturer’s one in terms of specificity. Therefore, the high agreement with the other methods used in the study and the good analytical performance demonstrated by the IDS-Euroimmun anti-tTG IgA ChLIA test confirm its suitability as a first-line screening test. The identification of possible IgA deficit in a single analytical step could allow for a sequential diagnostic approach, limiting total IgA testing to the identified subgroup of patients. Although the limitations of the study (small cohort, lack of clinical and histopathological data and of standardization in pre-characterization) call for prospective studies on larger cohorts of clinically characterized patients to confirm the results at the national level, the use of this test could standardize and optimize the CD diagnostic workflow reducing unnecessary tests and associated costs without compromising the diagnostic accuracy.