P294	Plasma concentrations of asymmetric dimethylarginine are associated with titers of anti-dsDNA antibodies, cardiovascular events and disease activity in patients with systemic lupus erythematosus.
T.Teerlink, I.Bultink, H.Heijst, B.Dijkmans, A.Voskuyl
VU University Medical Center, Amsterdam, NL.

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Traditional risk factors do not fully account for this elevated CVD risk. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is a novel risk factor for CVD. SLE is characterized by the presence of autoantibodies to double stranded DNA (anti-dsDNA). Anti-dsDNA has been shown to upregulate the methylation of protein arginine residues in vitro, which may lead to increased ADMA production. We have assessed the relation of plasma ADMA concentrations with anti-dsDNA titers, disease activity, organ damage and cardiovascular events in patients with SLE. Methods: In a cross-sectional design, demographic, clinical, and biochemical data were collected in 107 patients with SLE (98% female), with a mean (SD) age of 41 (13) years and mean disease duration of 7 (7) years. Results: Prevalent CVD was documented in 15% of the SLE patients and increased across tertiles of plasma ADMA concentrations (p for trend = 0.023). There was a significant positive association between ADMA concentrations and anti-dsDNA titers (r = 0.43; p<0.001). In a stepwise multivariate regression model with ADMA as dependent variable, high disease activity index score (p = 0.0001), high organ damage index score (p = 0.019), high anti-dsDNA titers (p = 0.006) and low HDL-cholesterol (p = 0.037) were independently associated with high plasma ADMA concentrations. Conclusions: In SLE patients, plasma ADMA concentrations were significantly associated with the prevalence of CVD, parameters of disease activity and organ damage. In addition, both in univariate and multivariate models, ADMA concentration was significantly associated with titers of anti-dsDNA. These autoantibodies have been shown to stimulate the expression of pro-inflammatory cytokines and we hypothesize that they play a dual role in the pathology of SLE by augmenting the inflammatory reaction and stimulating ADMA production.

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