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The Role of Innate and Adaptive Immunity to Oxidized Low‐Density Lipoprotein in the Development of Atherosclerosis
Author(s) -
KOBAYASHI KAZUKO,
LOPEZ LUIS R.,
SHOENFELD YEHUDA,
MATSUURA EIJI
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1361.086
Subject(s) - autoantibody , antibody , immunology , immune system , antiphospholipid syndrome , antigen , lipoprotein , acquired immune system , medicine , innate immune system , cholesterol
A bstract : 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), β2‐glycoprotein I (β2GPI) is a major antigenic target for anticardiolipin antibodies (aCLs). We recently reported that oxLDL interacts with β2GPI via oxLDL‐derived specific ligands, such as 7‐ketocholesteryl‐9‐caboxynonanoate (oxLig‐1) to form complexes. In vitro , anti‐β2GPI autoantibodies bind to oxLDL/β2GPI complexes that are actively taken up by macrophages via Fcγ receptors. Circulating oxLDL/β2GPI 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/β2GPI antibody levels in SLE patients with APS were significantly higher than those in SLE patients without APS and those in healthy individuals.