Binding of synthetic double-stranded DNA by serum from patients with systemic lupus erythematosus. Correlation with renal histology

Detection of antibody to double-stranded DNA by direct binding assays has proved useful in clinical management of patients with systemic lupus erythematosus (SLE). Recent confusion regarding specificity of these antibodies for SLE appe_.ars to be due, at least in part, to contamination of natural DNA preparations with non-double-stranded DNA antigens. Measurement of binding of a synthetic, self-complementary DNA copolymer (dAT) rather than of natural DNA (KB) has been shown to obviate some of these difficulties, apparently because of freedom of dAT from nondouble-stranded DNA antigens. Among the advantages found in this way was a higher degree of specificity of antibodies to double-stranded DNA for clinically-judged active lupus nephritis than had been suspected. Since activity of nephritis is difficult to assess clinically, histologic data were sought to confirm these observations. Thirty-two kidney specimens were examined by light and/or electron microscopy. The degree of histologic activity and the amount and location of glomerular electron-dense deposits were semiquantltated blindly. The binding of both dAT and KB DNA was measured by the ammonium sulfate method. Correlation with the amount of electron-dense deposits was highly significant for dAT binding and somewhat less so for KB DNA binding as determined by both parametric and nonparametric statistical methods. Significant correlation with histologic activity was found for dAT but not KB DNA binding. These results are consistent with previous data and suggest that dAT binding may provide a useful, noninvasive means of clinically assessing both nephritis activity and the intensity of glomerular immune-complex deposition as reflected by the amount of electron-dense deposits. If it can be confirmed that the latter provides long-term prognostic information, then dAT binding (and perhaps its reponse to therapy) may also prove of value in this regard.