OxLDL/β2GPI Complexes and Autoantibodies in Patients with Systemic Lupus Erythematosus, Systemic Sclerosis, and Antiphospholipid Syndrome: Pathogenic Implications for Vascular Involvement

摘要

Oxidized low-density lipoprotein (oxLDL) interacts with β2GPI, forming oxLDL/β2GPI complexes. Autoimmune vascular inflammation (and oxidative stress) may promote the formation of these complexes. The coexistence of oxLDL/β2GPI complexes with autoantibodies to these complexes suggests an active pro-atherogenic role in vascular thrombosis and atherosclerosis. Immunoglobulin G (IgG) anti-oxLDL/β2GPI antibodies have been regarded as pro-atherogenic, whereas IgM antibodies are thought to be anti-atherogenic. For this study, oxLDL/β2GPI complexes, IgG, and IgM anti-oxLDL/β2GPI 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/β2GPI 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/β2GPI antibody distribution followed the same pattern observed with oxLDL/β2GPI 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/β2GPI 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/β2GPI 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/β2GPI complexes and IgG anti-oxLDL/β2GPI antibodies indicate significant vascular oxidative stress as well as a possible pathogenic role in autoimmune-mediated atherosclerosis.