Plasma asymmetric dimethylarginine is related to anticitrullinated protein antibodies in rheumatoid arthritis of short duration

Abstract

We have recently demonstrated elevated plasma levels of an endogenous nitric oxide synthase inhibitor, asymmetric dimethyl- l-arginine (ADMA), and its association with carotid atherosclerosis in rheumatoid arthritis (RA). Both an elevated risk of myocardial infarction and increased levels of anticitrullinated protein antibodies (ACPAs), specific for RA, had been shown to precede the onset of clinical RA symptoms. Therefore, our aim was to verify the hypothesis that ADMA accumulation might accompany raised ACPAs titers in RA of short duration (≤3 years). Twenty patients (16 women, 4 men; mean age, 45 ± 12 years; mean disease duration, 2.3 ± 0.5 years) with active RA despite chronic disease-modifying antirheumatic medication, free of cardiovascular disease or atherosclerotic risk factors, were studied. Plasma levels of ADMA and its stereoisomer, symmetric dimethyl- l-arginine (SDMA), were assayed by liquid chromatography/tandem mass spectrometry. The ACPAs were measured by a second-generation enzyme-linked immunosorbent assay. In addition to routine biochemical assays, plasma concentrations of tumor necrosis factor α, monocyte chemoattractant protein–1, and vascular cell adhesion molecule–1 soluble form were analyzed with respective enzyme-linked immunosorbent assays. A significant positive correlation between levels of ACPAs and ADMA ( r = .60, P = .005), but not SDMA ( r = −.02, P = .9), was found. Neither ADMA nor SDMA was correlated to any of the clinical or biochemical parameters reflecting disease activity and inflammatory activation. Thus, excessive ADMA accumulation accompanies elevated ACPAs levels in patients with RA of short duration free of cardiovascular disease or risk factors.