The role of innate and adaptive immunity to oxidized low-density lipoprotein in the development of atherosclerosis.
Atherosclerosis is a chronic inflammatory process of the arterial wall associated with systemic and local immune responses to various antigens, oxidized low-density lipoprotein (oxLDL) being the most significant. Both IgM and IgG antibodies to oxLDL are produced during atherosclerosis. Some studies have shown that elevated levels of antibody to oxLDL correlate with the degree of atherosclerosis. Other studies reported that immunization of experimental animals with oxLDL induces high levels of antibodies to oxLDL, with decreased atherosclerosis, suggesting that the immune response to oxLDL may be antiatherogenic. The accelerated development of atherosclerosis has been observed in patients with systemic autoimmune diseases. In patients with antiphospholipid syndrome (APS), beta2-glycoprotein I (beta2GPI) is a major antigenic target for anticardiolipin antibodies (aCLs). We recently reported that oxLDL interacts with beta2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) to form complexes. In vitro, anti-beta2GPI autoantibodies bind to oxLDL/beta2GPI complexes that are actively taken up by macrophages via Fcgamma receptors. Circulating oxLDL/beta2GPI complexes were detected in patients with systemic lupus erythematosus (SLE) and APS, at higher levels than in healthy individuals. Autoantibodies against these complexes were also present; however, IgG anti-oxLig-1/beta2GPI antibody levels in SLE patients with APS were significantly higher than those in SLE patients without APS and those in healthy individuals.
Kobayashi
Kazuko
K
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Lopez
Luis R
LR
Shoenfeld
Yehuda
Y
Matsuura
Eiji
E
D000818:Animals; D016736:Antiphospholipid Syndrome / Q000276:immunology; D050197:Atherosclerosis / Q000209:etiology*; D001323:Autoantibodies / Q000502:physiology; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein