Antiphospholipid antibodies in arterial thrombosis

The high correlation between the IgG isotype of anticardiolipin antibodies (aCLs) and clinical thrombosis was first documented in 1983, and this obser vation was confirmed in subsequent studies. In addition, the frequency of f etal loss and thrombocytopenia was increased in this group of patients. The se findings were termed the antiphospholipid syndrome (APS). This syndrome was mostly seen in patients with systemic lupus erythematosus (SLE), but it soon became clear that also other patients not suffering from defined SLE might exhibit features of APS. aCL in APS patients are detected in immunoas says by using solid phase cardiolipin as a putative antigen. However, antib odies directed against phospholipid-binding plasma or serum proteins, beta2 -glycoprotein I (beta2-GPI), in particular, are also detected. Many recent studies have indicated that one of predominant antibodies that has been ide ntified as aCL in APS patients is against beta2-GPI rather than any of the negatively charged phospholipids. The epitopes recognized by anti-beta2-GPI antibodies raised in APS patients are composed of discontinuous amino acid sequences from the IV domain of human beta2-GPI. These epitopes are crypti c when beta2-GPI does not interact with anionic phospholipids. An early eve nt in atherosclerosis is the accumulation of cholesterol-laden foam cells, which originate mainly from monocyte-macrophage cells by their uptake of ch emically modified low-density lipoprotein (LDL). We found that beta2-GPI bi nds directly to oxLDL, and that the complex of oxLDL and beta2-GPI is subse quently recognized by aCL (anti-beta2-GPI) to be taken up by macrophages. W hile the pathogenesis of this accelerated atherosclerosis is likely to be m ultifactorial, it is possible that antiphospholipid antibodies, including a CL (anti-beta2-GPI antibodies), may have contributed to the formation of at herosclerotic lesion.