Lopez Luis R, Simpson Daniel F, Hurley Beth L, Matsuura Eiji
Corgenix Inc., 12061 Tejon Street, Westminster, CO 80234, USA.
Ann N Y Acad Sci. 2005 Jun;1051:313-22. doi: 10.1196/annals.1361.073.
Oxidized low-density lipoprotein (oxLDL) interacts with beta2GPI, forming oxLDL/beta2GPI complexes. Autoimmune vascular inflammation (and oxidative stress) may promote the formation of these complexes. The coexistence of oxLDL/beta2GPI complexes with autoantibodies to these complexes suggests an active pro-atherogenic role in vascular thrombosis and atherosclerosis. Immunoglobulin G (IgG) anti-oxLDL/beta2GPI antibodies have been regarded as pro-atherogenic, whereas IgM antibodies are thought to be anti-atherogenic. For this study, oxLDL/beta2GPI complexes, IgG, and IgM anti-oxLDL/beta2GPI antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Measurements were taken in two patient groups: (1) those with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA); and (2) those with primary and secondary antiphospholipid syndrome (APS). For oxLDL/beta2GPI complexes, SLE and SSc patients had the highest mean optical densities (ODs) (P <.001), followed by RA (P = .139) and healthy controls. IgG anti-oxLDL/beta2GPI antibody distribution followed the same pattern observed with oxLDL/beta2GPI complexes, SLE and SSc (P <.001), RA (P = .08), and controls. IgM antibodies showed a reverse pattern, with the highest mean OD in RA (P <.001), followed by SSc (P = .007) and SLE (P = 143). Both IgG and IgM anti-oxLDL/beta2GPI antibodies were significantly higher in secondary APS patients compared with SLE controls without APS. In addition, the highest mean OD and prevalence of IgG anti-oxLDL/beta2GPI antibodies were observed in APS patients with a history of arterial thrombosis. These results may reflect the widespread vascular involvement seen in SLE and SSc, in contrast to the relatively low vascular involvement in RA. In SLE and SSc, high serum levels and prevalence of circulating oxLDL/beta2GPI complexes and IgG anti-oxLDL/beta2GPI antibodies indicate significant vascular oxidative stress as well as a possible pathogenic role in autoimmune-mediated atherosclerosis.
氧化型低密度脂蛋白（oxLDL）与β2糖蛋白I（β2GPI）相互作用，形成oxLDL/β2GPI复合物。自身免疫性血管炎症（以及氧化应激）可能促进这些复合物的形成。oxLDL/β2GPI复合物与针对这些复合物的自身抗体共存，提示其在血管血栓形成和动脉粥样硬化中具有积极的促动脉粥样硬化作用。免疫球蛋白G（IgG）抗oxLDL/β2GPI抗体被认为具有促动脉粥样硬化作用，而IgM抗体则被认为具有抗动脉粥样硬化作用。在本研究中，采用酶联免疫吸附测定（ELISA）法检测oxLDL/β2GPI复合物、IgG和IgM抗oxLDL/β2GPI抗体。检测了两组患者：（1）患有系统性红斑狼疮（SLE）、系统性硬化症（SSc）和类风湿关节炎（RA）的患者；（2）患有原发性和继发性抗磷脂综合征（APS）的患者。对于oxLDL/β2GPI复合物，SLE和SSc患者的平均光密度（OD）最高（P<.001），其次是RA患者（P = .139）和健康对照者。IgG抗oxLDL/β2GPI抗体的分布与oxLDL/β2GPI复合物的分布模式相同，SLE和SSc患者（P<.001）、RA患者（P = .08）和对照者。IgM抗体呈现相反的模式，RA患者的平均OD最高（P<.001），其次是SSc患者（P = .007）和SLE患者（P = 143）。与无APS的SLE对照患者相比，继发性APS患者的IgG和IgM抗oxLDL/β2GPI抗体均显著更高。此外，在有动脉血栓形成病史的APS患者中，观察到IgG抗oxLDL/β2GPI抗体的平均OD和患病率最高。这些结果可能反映了SLE和SSc中普遍存在的血管受累情况，与之形成对比的是RA中相对较低的血管受累情况。在SLE和SSc中，循环oxLDL/β2GPI复合物和IgG抗oxLDL/β2GPI抗体的高血清水平和患病率表明存在显著的血管氧化应激以及在自身免疫介导的动脉粥样硬化中可能的致病作用。
