␤ 2 -glycoprotein I ( ␤ 2 -GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported ( J. Lipid Res ., 42: 697, 2001; J. Lipid Res. , 43: 1486, 2002) that ␤ 2 -GPI specifically binds to Cu 2 ؉ -oxidized LDL (oxLDL) and that the ␤ 2 -GPI ligands are -carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with ␤ 2 -GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the -carboxyl function of the ␤ 2 -GPI ligands was necessary for ␤ 2 -GPI binding. The ligand-mediated noncovalent interaction of ␤ 2 -GPI and oxLDL undergoes a temperature-and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable ␤ 2 -GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence of ␤ 2 -GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing ␤ 2 -GPI or LDL. Thus, the ␤ 2 -GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogene-

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