Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus

Anti-double stranded (dsDNA) antibodies are of considerable diagnostic valu e and are thought to be involved in the pathogenesis of systemic lupus eryt hematosus (SLE). Fluctuations in anti-dsDNA antibody levels are also used a s markers for disease activity and exacerbations. In this study we sought t o evaluate the anti-dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified wit h stored serum samples available prior to diagnosis within the US Departmen t of Defense serum repository. All 633 sera available from these patients w ere screened for anti-dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti-dsDNA a ntibodies prior to SLE diagnosis. The onset of anti-dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean o nset 2.7 years before diagnosis). In order to assess for fluctuations in an ti-dsDNA levels relative to diagnosis, cases were selected with at least tw o positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples availabl e shortly after diagnosis (less than or equal to 6 months) for comparison. Fifty eight percent of the 26 cases developed a significant rise in anti-ds DNA antibody levels within 6 months of diagnosis. A significant decline in anti-dsDNA levels ensued after diagnosis (and following treatment with cort icosteroids) in all seven cases with samples available. Patients with a sig nificant rise in anti-dsDNA antibodies at diagnosis were more likely to hav e renal disease than those who did not (66.7% compared to 27.3%, chi (2) =3 .94, P<0.05). These data suggest that anti-dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the d ata are consistent with increases in anti-dsDNA levels contributing to the onset of clinical illness in some patients with SLE.