Diagnosis of Antiphospholipid Syndrome by Chemiluminescent or Enzyme-Linked Immunosorbent Assay - A Comparison Study and Comprehensive Literature Review

Objective: Enzyme-linked immunosorbent assay (ELISA) is the established method for detecting antiphospholipid antibodies (aPL) in the diagnosis of antiphospholipid syndrome (APS) but is labor-intensive compared with the newer automated chemiluminescent assay (CLIA). This study aims to evaluate CLIA versus ELISA for aPL, correlate each method with clinical manifestations and perform a comprehensive literature review. Methods: Patient samples were concurrently tested by ELISA (QUANTA Lite (R)) and CLIA (ACL AcuStar (R)) for anti-cardiolipin antibody (aCL) and anti-beta 2-glycoprotein-I (a beta 2GPI) IgG and IgM. Assay results were correlated with any of the revised Sapporo APS clinical criteria. Results: Of the 107 patients, 67% fulfilled at least one clinical criterion. 38 patients (35.5%) had APS. For aCL IgG, aCL IgM and a beta 2GPI IgM, CLIA showed above 77% concordance and fair to excellent agreement (Cohen's kappa 0.39-0.86) with moderate/high positive ELISA of >= 40 units. Both methods showed good correlation (Spearman's r 0.60-0.80, p < 0.0001) that was non-linear over the range of titers. CLIA sensitivity and specificity was 46%-100% and 68%-95%, with AUROC ranging from 0.80-0.93. For a beta 2GPI IgG, concordance was 36.7% and agreement was low (kappa -0.23). Correlation with clinical criteria revealed no statistically significant difference in the occurrence of clinical manifestations in ELISA-positive versus CLIA-positive groups. Conclusions: aPL detection by CLIA showed close but incomplete concordance with ELISA. CLIA positivity correlated well with moderate/high ELISA positivity, but antibody titers should not be directly compared across systems. CLIA is an acceptable alternative to ELISA in the routine non-research setting. Our findings are congruent with the reviewed literature.