Enhanced monocyte expression of tissue factor by oxidative stress in patients with antiphospholipid antibodies: effect of antioxidant treatment

Summary. In a first study, we performed a cross‐sectional analysis of urinary excretion of isoprostanes, IPF_2α‐III and _VI, and monocyte tissue factor (TF) antigen and activity between 11 antiphospholipid (APL) antibody‐positive patients and 13 APL negative subjects. In a second study, 11 APL positive patients were randomly supplemented either with (n = 6) or without (n = 5) antioxidants (vitamin E at 900 IU day^?1, vitamin C at 2000 mg day^?1) for 6 weeks. In a third study, TF and superoxide anion were measured in human monocytes incubated with anti‐β₂ glycoprotein 1 (β₂GP₁) or control IgG, either with or without vitamin E. APL‐positive patients had higher values of isoprostanes (P < 0.05) and monocyte TF antigen (P = 0.001) and activity (P = 0.0001) than APL‐negative subjects. Only in APL positive patients did monocyte TF antigen correlate significantly with IPF_2α‐III (rho 0.79; P < 0.003) and IPF_2α‐VI (rho = 0.87; P < 0.0001). In patients who received antioxidant supplementation, we found a significant decrease of isoprostanes (P < 0.05) and monocyte TF antigen (P < 0.01) and activity (P < 0.007). In vitro experiments demonstrated that anti‐β₂GP₁ antibodies dose‐dependently enhanced the monocyte production of the superoxide anion and TF, which were significantly inhibited by vitamin E. This study demonstrates that in APL‐positive patients, oxidative stress contributes to activate the clotting system via over‐expression of monocyte TF. We suggest that anti‐β₂GP₁ antibodies could play a pivotal role by enhancing the monocyte production of oxygen free radicals.