Relationship between anti–double‐stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

Abstract

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-

Altered lipid raft–associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus

“…Indeed, there is evidence that some immune system abnormalities in SLE correlate with individual clinical features. For example, anti-dsDNA autoantibodies correlate with nephritis (39).…”

Re-biopsy in lupus nephritis

“…3 Many of these are mild, but repeated flares may end up in renal failure. 3 The classes of lupus nephritis 4 guide the treatment and prognosis and may change from one to another during a disease flare-up.…”

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

“…The patients with PLN had a higher SLEDAI score than the controls (median [25%, 75%], 16 [12,22] versus 10 [6,14]) but had the same median SLEDAI as the control group when limited to only extrarenal SLE manifestations (10 [4, 14] versus 10 [6,14]). NIH Activity and Chronicity Index scores (median [25%, 75%]) were 8 (5, 10) and 3 (1, 3), respectively ( Table 1).…”