Matsuura Eiji, Kobayashi Kazuko, Koike Takao, Shoenfeld Yehuda
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Autoimmun Rev. 2002 Dec;1(6):348-53. doi: 10.1016/s1568-9972(02)00084-8.
Beta2-glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). Oxidized low-density lipoprotein (oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI autoantibodies. Ligands specific for beta2-GPI derived from oxLDL have been characterized as oxidized forms of cholesteryl linoleate, such as 7-ketocholesterol-9-carboxynonanoate, i.e. 9-oxo-9-(7-ketocholest-5-en-3beta-yloxy) nonanoic acid, (namely oxLig-1). The in vitro phenomenon that it is significantly increased in binding of oxLig-1 containing liposomes to macrophages via an interaction with beta2-GPI and an anti-beta2-GPI autoantibody (via the Fcgamma receptor) may propose a novel mechanism on 'autoantibody-mediated atherosclerosis'. Furthermore, autoantibodies against a complex of beta2-GPI and oxLig-1 are detected in sera of APS patients and appearance of the antibodies is associated with episodes of thrombosis, especially, arterial thrombosis. Thus, autoimmune atherogenesis linked to beta2-GPI interaction with oxLDL and autoantibodies may be present in APS.
β2-糖蛋白I（β2-GPI）是抗磷脂综合征（APS）患者体内抗磷脂抗体（aPL）的主要抗原。氧化型低密度脂蛋白（oxLDL）随后成为β2-GPI和抗β2-GPI自身抗体的作用靶点。源自oxLDL的β2-GPI特异性配体已被鉴定为亚油酸胆固醇酯的氧化形式，如7-酮胆固醇-9-羧基壬酸，即9-氧代-9-（7-酮胆甾-5-烯-3β-基氧基）壬酸（即oxLig-1）。通过与β2-GPI和抗β2-GPI自身抗体（通过Fcγ受体）相互作用，含oxLig-1的脂质体与巨噬细胞的结合在体外显著增加，这一现象可能提示了“自身抗体介导的动脉粥样硬化”的新机制。此外，在APS患者血清中检测到针对β2-GPI和oxLig-1复合物的自身抗体，且这些抗体的出现与血栓形成事件相关，尤其是动脉血栓形成。因此，与β2-GPI与oxLDL及自身抗体相互作用相关的自身免疫性动脉粥样硬化可能存在于APS中。
