Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies.
The mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythematosus have been studied. Seventeen (56.6%) were positive for aPL because they had lupus anticoagulant and/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF ) and urinary excretion of two isoprostanes, 8-epi-PGF2alpha and IPF2alpha -I, free radical catalyzed oxidation products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF2alpha and IPF2alpha -I than controls; urinary excretion of the two isoprostanes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF2alpha was highly correlated with both aCL titer (Rho = 0. 70, P < .0001) and TNF (Rho = 0.84, P < .0001), a measure of disease severity. Excretion of this isoprostane was also higher in those patients who exhibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2alpha -I. No difference of 8-epi-PGF2alpha was observed between patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and increased 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.
Iuliano
L
L
The Institute of Clinical Medicine I, University "La Sapienza," Rome, Italy; and The Center for Experimental Therapeutics, The University of Pennsylvania, Philadelphia, PA, USA.
Praticò
D
D
Ferro
D
D
Pittoni
V
V
Valesini
G
G
Lawson
J
J
FitzGerald
G A
GA
Violi
F
F
D000293:Adolescent; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000276:immunology*; D016718:Arachidonic Acid / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid