The immunology of atherothrombosis in the antiphospholipid syndrome: antigen presentation and lipid intracellular accumulation.
The antiphospholipid syndrome (APS), characterized by elevated serum levels of antiphospholipid antibodies (aPL) and thromboembolic complications, is a common cause of acquired hypercoagulability. The plasma protein beta2-glycoprotein I (beta2GPI) is the most clinically relevant antigenic target for aPL. Recent experimental evidence from our laboratory substantiated the concept that IgG anti-beta2GPI immune complexes containing oxidized LDL (oxLDL) not only facilitated the intracellular accumulation of oxLDL in macrophages but also allowed the presentation of beta2GPI epitopes to pathogenic autoreactive T cells. Both mechanisms required FcgammaRI-mediated uptake by macrophages/monocytes. Furthermore, several clinical studies demonstrated that the presence of circulating oxLDL/beta2GPI complexes and IgG autoantibodies to these complexes was significantly associated with vascular inflammation (i.e. autoimmune-mediated atherothrombosis) in autoimmune patients. In this article, we review recent findings concerning the biochemical and immunologic mechanisms involved in autoimmune-mediated atherothrombosis in patients with APS.
Matsuura
Eiji
E
Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. eijimatu@md.okayama-u.ac.jp
Kobayashi
Kazuko
K
Matsunami
Yukana
Y
Lopez
Luis R
LR
D017152:Antibodies, Antiphospholipid / Q000097:blood; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D001158:Arteries / Q000276:immunology* / Q000473:pathology; D001324:Autoantigens / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D017452:Receptors, IgG / Q000378:metabolism; D019851:Thrombophilia; D013927:Thrombosis / Q000276:immunology* / Q000473:pathology; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D000936:Antigen-Antibody Complex; D001324:Autoantigens; C489017:FCGR1A protein, human; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein