ENHANCED LIPID-PEROXIDATION IN PATIENTS POSITIVE FOR ANTIPHOSPHOLIPIDANTIBODIES

The mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown, Because an in vitro study suggested that aPL m ay derive from pro-oxidant conditions, we sought a relationship betwee n aPL and isoprostanes, indices of lipid peroxidation in vivo, Thirty patients with systemic lupus erythematosus have been studied. Seventee n (56.6%) were positive for aPL because they had lupus anticoagulant a nd/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF) and urinary excretion of two isoprostanes , 8-epi-PGF(2 alpha) and IPF2 alpha-I, free radical catalyzed oxidatio n products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF(2 alpha) and IPF2 alpha-I than controls; urinary excretion of the two isoprost anes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF( 2 alpha) was highly correlated with both aCL titer (Rho = 0.70, P < .0 001) and TNF (Rho = 0.84, P < .0001). a measure of disease severity. E xcretion of this isoprostane was also higher in those patients who exh ibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2 alpha-I. No difference of 8-epi-PGF,, was observed b etween patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and in creased in vivo lipid peroxidation, supports the hypothesis that these antibodies may result from pro-oxidative conditions and suggests that inflammation may play an important role. (C) 1997 by The American Soc iety of Hematology.