BACKGROUND: Autoantibody specificity in autoimmune diseases is variable due to each patient's individual spectrum of autoantibodies and the inherent differences between detection methods and tests. Since false-positive results have downstream consequences, we conducted a comprehensive assessment of anti-double stranded DNA (anti-dsDNA) specificity from published studies of systemic lupus erythematosus (SLE). METHODS: A systematic review (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects) identified cross-sectional or case-control studies published January 2004 to August 2019, reporting anti-dsDNA test accuracy data in SLE. Study quality was assessed using Quality Assessment Tool for Diagnostic Accuracy Studies, version 2. A meta-analysis was conducted to estimate specificity by test method or named test where feasible. RESULTS: Thirty studies were included covering 43 different tests. The Crithidia luciliae indirect immunofluorescence test (CLIFT) and fluorescence enzyme immunoassay methods are likely to be ≥ 90% specific (Euroimmun 97.8% (95% CI 96.2%-98.7%) 4 studies; EliA 94.7% (95% CI 91.7%-96.7%), 6 studies; CLIFT 98.7% (95% CI 96.7%-99.5%), 8 studies/7 tests]. For other test methods, specificity was not fully demonstrated to be ≥ 90% and/or the control group included healthy patients possibly overestimating specificity. More studies are required for NOVA Lite [96.0% (95% CI 87.2%-98.9%), 5 studies], chemiluminescence immunoassays [92.3% (95% CI 83.6%-96.6%), 6 studies/4 tests], multiplex immunoassays [89.3% (95% CI 86.1%-91.8%), 4 studies/2 tests], and Farr fluorescent immunoassays (no estimate, 2 studies). Specificity data reported for Farr radioimmunoassays [93.8% (95% CI 85.4-97.5%), 11 studies, 9 tests] and enzyme-linked immunosorbent assays [93.4% (95% CI 89.9%-95.7%), 15 studies/16 tests] lacked consistency. CONCLUSION: Anti-dsDNA testing shows considerable variation in test specificity, with potential impact on the management of SLE patients. This review may help laboratory specialists and clinicians choose and interpret the appropriate anti-dsDNA test for their setting.
Carmen Andalucía (formerly Thermo Fisher Scientific) assisted with the systematic review, project design, and data validation. Mark Orme (ICERA Consulting Ltd) aided with the systematic literature review (August 2019), and with drafting and proofreading this article. We would like to thank Dr Ghirardello, Division of Rheumatology, University of Padova, Italy for providing additional study data for this analysis.
© American Association for Clinical Chemistry 2021.