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  • Title: Antiphospholipid antibodies in arterial thrombosis.
    Author: Koike T.
    Journal: Ann Med; 2000 Dec; 32 Suppl 1():27-31. PubMed ID: 11209978.
    Abstract:
    The high correlation between the IgG isotype of anticardiolipin antibodies (aCLs) and clinical thrombosis was first documented in 1983, and this observation was confirmed in subsequent studies. In addition, the frequency of fetal loss and thrombocytopenia was increased in this group of patients. These 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 immunoassays by using solid phase cardiolipin as a putative antigen. However, antibodies 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 identified 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 cryptic when beta2-GPI does not interact with anionic phospholipids. An early event in atherosclerosis is the accumulation of cholesterol-laden foam cells, which originate mainly from monocyte-macrophage cells by their uptake of chemically modified low-density lipoprotein (LDL). We found that beta2-GPI binds directly to oxLDL, and that the complex of oxLDL and beta2-GPI is subsequently recognized by aCL (anti-beta2-GPI) to be taken up by macrophages. While the pathogenesis of this accelerated atherosclerosis is likely to be multifactorial, it is possible that antiphospholipid antibodies, including aCL (anti-beta2-GPI antibodies), may have contributed to the formation of atherosclerotic lesion.
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