Comparison of Five Assays for the Detection of Anti-dsDNA Antibodies and Their Correlation with Complement Consumption

<b>Background</b>: Anti-dsDNA is an important biomarker for the diagnosis, prognosis, and monitoring of systemic lupus erythematosus (SLE). Although several assays for anti-dsDNA antibody detection are routinely used, standardization remains limited, and differences have been reported. This study aimed to compare five methods for anti-dsDNA antibody detection and to estimate their association with complement consumption. <b>Methods</b>: A total of 149 samples submitted for routine laboratory testing were collected and tested on five platforms: <i>Crithidia luciliae</i> indirect immunofluorescence test (CLIFT), addressable laser bead immunoassay (ALBIA), a high-avidity (HA) enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay (CIA), and a novel particle-based multi-analyte technology (PMAT). Complements C3 and C4 were available for a subset of the total samples. <b>Results</b>: Correlation between anti-dsDNA assays ranged from 0.94 (CIA and PMAT) to 0.65 (ALBIA and CLIFT). The AUC from the ROC analysis using CLIFT as a reference was 0.95 for PMAT, 0.94 for CIA, 0.93 for ELISA, and 0.86 for ALBIA. The highest sensitivity relative to CLIFT at a fixed specificity of 94.4% was 84.7% for CIA and ELISA, 76.3% for PMAT, and 42.4% for ALBIA. Correlation between anti-dsDNA and C3 ranged from -0.81 for ELISA to -0.51 for ALBIA. <b>Conclusions</b>: Different anti-dsDNA detection methods showed varying diagnostic performance and correlation and varying agreement with CLIFT and complement consumption. ELISA, CIA, and PMAT showed high correlation to each other and to CLIFT and were in strong concordance with low C3 levels. In contrast, ALBIA revealed lower clinical performance and correlation with CLIFT and complement consumption.