Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials.Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer >15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used.Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P ‫؍‬ 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively).Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.Anti-double-stranded DNA (anti-dsDNA) antibodies are diagnostic for systemic lupus erythematosus (SLE) (1) and have been implicated in the underlying pathogenesis of SLE renal disease and other disease manifestations (2-7). Immune complexes containing anti-

, 5 and the LJP 394-90-09 Investigator ConsortiumObjective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-doublestranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare.Methods. We conducted a randomized, placebocontrolled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat ( Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced >50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P ‫؍‬ 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated.Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.There is a substantial body of evidence implicating anti-double-stranded DNA (anti-dsDNA) antibodies in the pathogenesis of lupus nephritis. Anti-dsDNA antibodies are rarely found in individuals without SLE (1-4), and their presence is diagnostic for SLE and prognostic for development of lupus nephritis. The presence of anti-dsDNA antibodies often correlates with active renal disease (5-8). Anti-dsDNA antibodies are concentrated in the kidneys of SLE patients and often have a much higher avidity for dsDNA than do antibodies in the circulation (9,10). Well-controlled studies have demonstrated a strong correlation between rises in anti-dsDNA antibody levels and subsequent exacerbations of . Similarly, reductions in antiClinicalTrials.gov identifier: NCT00035308.

Objective. To analyze clinical fluids for the presence of Borreliu butgdo#eri DNA using the polymerase chain reaction (PCR).Methods. We utilized a modified, nested PCR to detect the presence of Borreliu DNA in 99 samples of serum, urine, cerebrospinal fluid (CSF), or synovial fluid obtained from 44 patients with various stages of Lyme disease and 47 control subjects. Primer specificity was corroborated by examining 2 DNA data banks, testing against DNA from other organisms, and confirming results with a second set of nested primers.Results. Nested PCR was capable of detecting DNA from fewer than 10 organisms in 1 ml of fluid. The specificity of this technique was 96.4%, with a sensitivity of 76.7%. Although the specificity was uniformly high, the sensitivity was dependent upon the body fluid being tested: CSF loo%, urine loo%, synovial fluid 80%, and serum 59%. The rate of false-positive results was 3.6%.

The DNA methylation inhibitor 5-azacytidine induces autoreactivity in cloned CD4+ T cells, but the functional consequences of this response are unknown. We now report that CD4+ T cells treated with 5-azacytidine respond to autologous antigen-presenting cells and induce autologous B cell differentiation without exogenous antigen or mitogen. This mechanism could play a role in some autoimmune diseases characterized by T cell DNA hypomethylation and polyclonal B cell activation.