Auto-antibodies to double-stranded DNA as biomarker in systemic lupus erythematosus: comparison of different assays during quiescent and active disease.

Objective: Auto-antibodies directed to dsDNA (anti-dsDNA) are used in diagnosis and follow-up for SLE. However, multiple assays are used. The objective of this study was to determine the best-performing assays, especially in prediction of exacerbations.

Methods: Seven assays were compared during LN (n = 58). The two assays with the most frequent positive results during active nephritis were selected and tested in 152 SLE patients with quiescent disease, 40 with active disease and 214 disease controls. Furthermore, longitudinal samples of SLE patients with and without exacerbations were examined to determine the positive predictive value of an increase for an exacerbation.

Results: Of seven assays, results of the Farr (Siemens) and enzyme-labelled anti-isotype assay (EliA) (ThermoFisherScientific) were foremost associated with active nephritis (both 95%). Sensitivity in active SLE was equal using Farr or EliA (95 vs 93%). In quiescent disease, the specificity of EliA was higher (Farr: 53% vs EliA: 91%). In longitudinal analyses, a 25% increase of anti-dsDNA preceded an exacerbation in 75 vs 69% (Farr vs EliA). In SLE patients without exacerbations (n = 42), a rise was seen in 10 vs 12%. Increases in anti-dsDNA occurred more often prior to nephritis (n = 17) compared with non-nephritic flares (n = 17), which was not different between both assays (Farr: 82 and 66%, respectively; EliA: 93 and 43%, respectively).

Conclusion: Anti-dsDNA is most frequently positive using Farr and EliA during active nephritis, with comparable sensitivity. Both assays performed equally during exacerbations. However, EliA had higher specificity in quiescent disease and had several advantages, including no use of radioactive materials and less time required.