Clinical Information

Anti-double-stranded DNA (anti-dsDNA) antibodies are highly specific for systemic lupus erythematosus (SLE) and are offered in clinical laboratories for the evaluation at-risk patients and management of affected individuals.(1) Anti-dsDNA antibodies are also included in the classification criteria for SLE.(2,3) In addition to their use in SLE diagnostic evaluation, these autoantibodies are also associated with disease activity and lupus nephritis (LN).(4-7)These antibodies are detected and quantified using various methods and analytes to dsDNA.(8) The immunological response to dsDNA has been demonstrated to be diverse with different results reported between test systems probably due to multiple factors not limited to disease heterogeneity and the absence of assay harmonization.(4-8)

The frequently used methods for detection and quantification of anti-dsDNA antibody in the clinical laboratory include the solid-phase immunoassays (SPAs) such as the enzyme linked immunosorbent assay, fluoro-enzyme immunoassay, chemiluminescence immunoassay, multiplexed bead-based assays and indirect immunofluorescence test using Crithidia luciliae (CLIFT) as substrate. Due to its high specificity but low sensitivity, the CLIFT is widely used as a confirmatory test following a positive anti-dsDNA IgG result obtained in a SPA.(4-8) However, discordance of positivity between SPAs as well as SPAs and CLIFT for anti-dsDNA antibodies is relatively common (4-8), occurring in a fifth of patients overall and a third of visits (6). Although the performance between specific SPA and CLIFT vary, SPA positivity is generally associated with LN less often than CLIFT positivity.

With the significant discordance of results between anti-dsDNA antibody assays, obtaining both CLIFT and SPA may be beneficial for diagnosis and routine monitoring of SLE. Using two different methods in a panel for detecting anti-dsDNA antibodies at diagnosis is useful because it improves diagnostic sensitivity while maintaining high specificity, providing complementary information that a single assay alone might miss.(4-8) This combined approach enhances the overall diagnostic yield for SLE, particularly in identifying specific clinical features like LN.