Circulating DNA in systemic lupus erythematosus. Association with central nervous system involvement and systemic vasculitis

Circulating double-stranded DNA (dsDNA) in the form of immune complexes has long been thought to play an important pathogenetic role in systemic lupus erythematosus (SLE) glomerulonephritis. However, attempts to demonstrate circulating DNA in patients with SLE have led to conflicting conclusions, largely for technical reasons. Using methods designed to avoid these limitations it was previously shown that circulating DNA occurs infrequently if at all in normal subjects. Surprisingly, the same was reported to be true of unselected patients with SLE although sensitivity of the assay used was relatively low. Preliminary experiments in this laboratory, using an assay with improved sensitivity, suggested an association between circulating dsDNA and the relatively uncommon SLE manifestations of vasculitis and/or central nervous system (CNS) involvement. In the present study the possibility on this association was explored by prospectively classifying patients with active SLE into those with systemic vasculitis, CNS involvement or neither. Patients with other clinical states which themselves are known or believed to be associated with circulating DNA were excluded. Multiple plasma specimens from each patient were examined by a modified counterimmunoelectrophoresis (CIE) assay capable of detecting 20 to 50 ng/ml of dsDNA. Patients were considered to have circulating dsDNA only when the latter was demonstrated on multiple separate occasions. Of 20 patients with CNS involvement and/or systemic vasculitis, 16 had persistently circulating DNA. In contrast, one of 18 patients with active SLE but without these manifestations demonstrated circulating DNA, a highly significant difference. This association was also seen in longitudinal studies of four individual patients with SLE who had multiple episodes of activity, some of which included CNS involvement or vasculitis. Circulating dsDNA was not found in patients with active systemic inflammation alone or in those receiving corticosteroids or cytostatic agents. Similarly, differences in the prevalence of anti-dsDNA antibodies between the patient groups could not account for the results. Hence, it is concluded that persistently circulating dsDNA occurs specifically in patients with SLE who have vasculitis and CNS involvement. Furthermore, the prevalence of circulating dsDNA in patients with active SLE who lack these manifestations appears to be negligible within the limits of the assay used. Possible pathogenetic implications of these results are discussed.