Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome

Objective. To assess the role of nitrite (NO₂^-), nitrate (NO₃^-), and nitrative stress in thrombotic primary antiphospholipid syndrome (PAPS). Methods. We investigated 46 patients with PAPS: 21 asymptomatic but persistent carriers of antiphospholipid antibodies (PCaPL), 38 patients with inherited thrombophilia (IT), 33 patients with systemic lupus erythematosus (SLE), and 29 healthy controls (CTR). IgG anticardiolipin (aCL), IgG anti-beta₂-glycoprotein I (anti-β₂-GPI), IgG anti-high density lipoprotein (aHDL), IgG anti-apolipoprotein A-I (aApoA-I), crude nitrotyrosine (NT) (an indicator of nitrative stress), and high sensitivity C-reactive protein (CRP) were measured by immunoassays. Plasma nitrite (NO₂^-), nitrate (NO ₃^-), and total antioxidant capacity (TAC) were measured by colorimetric spectroscopic assays. Results. Average plasma NO₂ ^- was lower in PAPS, PCaPL, and IT (p < 0.0001); average NO ₃^- was highest in SLE (p < 0.0001), whereas average NT was higher in PAPS and SLE (p = 0.01). In thrombotic PAPS, IgG aCL titer and number of vascular occlusions negatively predicted NO₂^- (p = 0.03 and p = 0.001, respectively), whereas arterial occlusions and smoking positively predicted NO₃^- (p = 0.05 and p = 0.005), and CRP positively predicted NT (p = 0.004). In the PCaPL group IgG aCL negatively predicted NO₃^- (p = 0.03). In the SLE group IgG aCL negatively predicted NO₂^- (p = 0.03) and NO ₃^- (p = 0.02). Conclusion. PAPS is characterized by decreased NO₂^- in relation to type and number of vascular occlusions and to aPL titers. Nitrative stress and low grade inflammation are linked phenomena in PAPS and may have implications for thrombosis and atherosclerosis. The Journal of Rheumatology