Atherogenic autoantigen: oxidized LDL complexes with beta2-glycoprotein I

Immunobiology. 2003;207(1):17-22. doi: 10.1078/0171-2985-00214.

Abstract

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). In 1997, we demonstrated that beta2-GPI specifically binds to Cu2+-oxidized low-density lipoprotein (oxLDL) and that the beta2-GPI-oxLDL complex is subsequently targeted by anti-beta2-GPI antibodies in vitro. Then ligands for beta2-GPI were purified from oxLDL and characterized as omega-carboxylated 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) dodecanoate (oxLig-2). These ligands mediate to form oxLDL-beta2-GPI complexes, and the complexes are taken up avidly by macrophages via anti-beta2-GPI autoantibody-mediated phagocytosis. We recently demonstrated that appearance of autoantibodies against a complex of beta2-GPI and oxLig-1 are highly associated with a history of arterial thrombosis. Serum oxLDL-beta2-GPI complex and their IgG immune complexes are also risk factors arterial thrombosis in APS patients. There is increasing circumstantial evidence of autoimmune mechanism involving beta2-GPI and oxLDL in the atherogenesis in APS.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiphospholipid Syndrome / immunology
  • Arteriosclerosis / prevention & control
  • Autoantigens / immunology*
  • Glycoproteins / immunology
  • Glycoproteins / metabolism*
  • Humans
  • Ligands
  • Lipoproteins, LDL / immunology
  • Lipoproteins, LDL / metabolism*
  • Models, Biological
  • Models, Chemical
  • Oxygen / metabolism
  • Protein Binding
  • Risk Factors
  • Thrombosis / complications
  • beta 2-Glycoprotein I

Substances

  • Autoantigens
  • Glycoproteins
  • Ligands
  • Lipoproteins, LDL
  • beta 2-Glycoprotein I
  • oxidized low density lipoprotein
  • Oxygen