The role of innate and adaptive immunity to oxidized low-density lipoprotein in the development of atherosclerosis

Kazuko Kobayashi, Luis R. Lopez, Yehuda Shoenfeld, Eiji Matsuura

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Atherosclerosis is a clironic 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 P2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-cabosynonanoate (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.

Original languageEnglish
Pages (from-to)442-454
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1051
DOIs
Publication statusPublished - 2005

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Adaptive Immunity
Innate Immunity
Atherosclerosis
Antiphospholipid Syndrome
Glycoproteins
Systemic Lupus Erythematosus
Antibodies
LDL Lipoproteins
Autoantibodies
oxidized low density lipoprotein
Immunity
Immunization
Anticardiolipin Antibodies
Fc Receptors
Macrophages
Autoimmune Diseases
Immunoglobulin M
Animals
Immunoglobulin G
Ligands

Keywords

  • β2-glycoprotein I
  • Antiphospholipid syndrome
  • Oxidized low-density lipoprotein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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abstract = "Atherosclerosis is a clironic 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 P2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-cabosynonanoate (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.",
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N2 - Atherosclerosis is a clironic 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 P2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-cabosynonanoate (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.

AB - Atherosclerosis is a clironic 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 P2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-cabosynonanoate (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.

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