High-affinity autoantibodies to dsDNA (double-stranded DNA) detected by the Farr method (ammonium sulfate precipitation) and quantitated in IU/mL by reference to Wo-80, the ultimate international standard,¹ are reliably predictive of SLE when present in high concentration.^1,2 Indeed, about two-thirds of patients without clinical SLE but with Farr-assay-detectable anti-dsDNA autoantibodies will develop SLE within a year after detection of the autoantibodies.³ The Crithidia IFA test and currently available EIAs measure dsDNA autoantibodies of various affinities and yield many positive and, hence, confusing results in patients without SLE.⁴ Detection of autoantibodies to ssDNA has no clinical utility except perhaps as a general screen for autoantibodies, e.g., in chronic liver disease.⁵

Concentrations of dsDNA autoantibodies are higher in patients with flares of SLE.^6-8 The predictive value of increases in dsDNA autoantibodies for disease flares (doubling within 10 weeks⁷ or an increase of 30 IU/mL or an increase of 25% from the lowest value over the preceding four months⁸) is over 90%.^7-8 These predictive values are influenced by the organ(s) involved in the flare⁶ and probably by the immunogenetics of the individual which influences the immune response in such situations. Indeed, low-avidity anti-dsDNA autoantibodies are more common than high-avidity anti-dsDNA autoantibodies in SLE patients with CNS involvement.^2,4 Hence, simultaneous or serial measurement of low- (EIA) and high-avidity (Farr) dsDNA autoantibodies might help identify subsets of SLE in which one type of assay (e.g., EIA vs. Farr) might be more useful for monitoring.^2,4

Despite lingering doubts about the precise predictive value of changes in dsDNA autoantibody concentrations for flares in different organ systems,⁶ detection of a 25% increase compared with the previous sample (which contained at least 15 IU/mL) followed by increased prednisone treatment based on those increases is associated with a decreased number of flares compared to a control group treated conventionally.⁹

In patients with suspected SLE, assays for autoantibodies to dsDNA (Farr) and to Sm (EIA with IB confirmation) should both be sought, because sera from such patients can contain either or both of these autoantibodies which are essentially diagnostic of SLE.¹⁰

Consensus sera are now available to clinical laboratories and vendors for use in the detection of double-stranded DNA, Jo-1, SS-A, SS-B, Sm, U1-RNP, Scl-70 and centromere antibodies to help evaluate and improve current EIA methods.¹¹

Plasma levels of soluble CD154 correlated with the titers of anti-dsDNA antibody and with clinical disease activity. Elevated expression of sCD154 may contribute to immune activation of APCs and stimulation of autoantibody-producing B cells in patients with SLE.¹²

Recent evidence suggests that autoantibodies to dsDNA may be induced by an infectious agent, which in turn could extend the immunologic response to endogenous nuclear antigens. Therefore, sequence-specific anti-dsDNA B-cells could provide the stimulus to break tolerance to self.¹³