Lipid peroxidation occurs frequently in patients with systemic autoimmune diseases and contributes to autoimmune vascular inflammation. Oxidized low-density lipoprotein (oxLDL) interacts with β2-glycoprotein I (β2GPI), forming oxLDL/β2GPI complexes. Circulating oxLDL/β2GPI complexes and autoantibodies to these complexes have been demonstrated in patients with systemic lupus erythematosus and antiphospholipid syndrome. These findings suggest an immunogenic nature of the complexes and an active proatherogenic role in autoimmunity. Biochemical characterization of the complexes and immunohistochemical studies of atherosclerotic lesions suggest that most of the complexes originate in the arterial wall and are released into circulation. The in vitro macrophage uptake of oxLDL/β2GPI complexes increased significantly in the presence of antiphospholipid antibodies (anti-β2GPI), suggesting that macrophage Fcγ receptors are involved in the lipid intracellular inflthat leads to foam cell formation. These findings provide an immunologic explanation for the accelerated development of atherosclerosis seen in systemic lupus erythematosus and antiphospholipid syndrome. © Springer Science+Business Media, LLC 2009.