Matsuura E, Kobayashi K, Inoue K, Lopez L R, Shoenfeld Y
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Lupus. 2005;14(9):736-41. doi: 10.1191/0961203305lu2211oa.
beta2-glycoprotein I (beta2GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with beta2GPI and immunoreactive lymphocytes. oxLDL/beta2GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti-oxLDL/beta2GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/beta2GPI complexes were internalized by macrophages via IgG anti-beta2GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.
β2糖蛋白I（β2GPI）是抗磷脂抗体的主要抗原靶点。氧化型低密度脂蛋白（oxLDL）是动脉粥样硬化病变中发现的主要脂蛋白，它与β2GPI和免疫反应性淋巴细胞共定位。oxLDL/β2GPI复合物出现在患有系统性红斑狼疮（SLE）、抗磷脂综合征（APS）、系统性硬化症、糖尿病和慢性肾病等疾病患者的血液循环中。因此，这些复合物可能与血管系统的全身性和慢性炎症有关。IgG抗oxLDL/β2GPI复合物自身抗体及其免疫复合物仅在SLE/APS患者及其动物模型中被检测到，并且与动脉血栓形成密切相关。oxLDL/β2GPI复合物通过IgG抗β2GPI抗体介导的吞噬作用被巨噬细胞内化。相比之下，源自高脂血症小鼠的IgM抗oxLDL抗体降低了动脉粥样硬化的发生率。患者体内IgG和IgM抗oxLDL抗体的分布模式表明了这些抗体的不同作用。
