beta 2-Glycoprotein I (beta 2-GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). We previously reported that beta 2-GPI specifically binds to oxidized low-density lipoprotein (oxLDL). Further, a ligand specific for beta 2-GPI, oxLig-1, purified from the extracted lipids of oxLDL was identified as 7-ketocholesterol-9-carboxynonanoate (i.e., 9-oxo-9-(7-ketocholest-5-en-3 beta-yloxy) nonanoic acid) OxLig-1 was recognized by beta 2-GPI and subsequently by anti-beta 2-GPI autoantibodies. Binding of liposomes containing oxLig-1 to macrophages were significantly enhanced in the presence of both beta 2-GPI and an anti-beta 2-GPI autoantibody derived from (NZW x BXSB) F1 mouse, an animal APS model, or from APS patients. Anti-beta 2-GPI autoantibodies derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase beta 2-GPI complex with oxLig-1. It was also reported that LDL-receptor-deficient mice that were fed a chow diet and immunized with beta 2-GPI had an accelerated atherosclerosis and that beta 2-GPI was abundantly expressed within subendothelial regions and intimal-medial borders of human atherosclerotic plaques. All of these observations strongly suggest that autoimmune atherogenesis linked to beta 2-GPI interaction with oxLDL and autoantibodies may be present in APS.
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http://dx.doi.org/10.1080/08830180210414 | DOI Listing |
Front Immunol
December 2024
Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
Introduction: Unfolded Von Willebrand Factor (VWF) is increased in thrombotic pathologies such as myocardial infarction. Unfolded VWF mediates the binding of platelets without the need for collagen. β-glycoprotein I (β-GPI) is a natural inhibitor of the platelet-VWF interaction.
View Article and Find Full Text PDFClin Exp Rheumatol
January 2025
Laboratoire d'Immunologie, AP-HP, Hôpital Européen Georges Pompidou, Paris; and Inflammation, Complement, and Cancer, Université Paris Cité, INSERM, UMRS 1138, Cordeliers Research Center, Team Paris, France.
Objectives: Antiphospholipid syndrome (APS) is an autoimmune disease combining the occurrence of thrombotic and/or obstetric events with the persistent presence of antiphospholipid antibodies (i.e. lupus anticoagulant (LA), anti-cardiolipin (aCL) and anti-beta-2-glycoprotein I (aβ2GPI) antibodies).
View Article and Find Full Text PDFClin Appl Thromb Hemost
December 2024
Division of Haematology, Department of Pathology, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by antiphospholipid antibodies associated with thrombosis and pregnancy complications. Catastrophic APS is a severe form involving multiple organ systems with a high mortality rate. The pathogenesis involves antiphospholipid antibodies which target phospholipid-binding proteins and damage endothelial cells thus activating coagulation, triggering a pro-thrombotic state.
View Article and Find Full Text PDFLupus Sci Med
December 2024
Division of Hematology and Hematologic Malignancies, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
Objectives: Antiphospholipid syndrome (APS) is characterised by the presence of antiphospholipid antibodies (aPLs) and clinical outcomes of thrombosis and/or obstetric morbidity and is associated with systemic lupus erythematosus (SLE). IgG antiphosphatidylserine/prothrombin complex (aPS/PT), IgM aPS/PT and IgG anti-beta 2 glycoprotein 1-domain 1 (aβ2GP1-D1) are novel aPLs that have been associated with thrombosis; however, conclusive data are still lacking. It remains unclear how best to incorporate non-criteria autoantibodies into clinical decision-making.
View Article and Find Full Text PDFObstet Gynecol
January 2025
University of Utah and ARUP Laboratories, Salt Lake City, and Intermountain Health, Murray, Utah; the Hospital for Special Surgery, New York, New York; and Oregon Health & Science University, Portland, Oregon.
Objective: To investigate the value of anti-β2 glycoprotein-I domain 1 (aD1) and antiphosphatidylserine-prothrombin antibodies for predicting adverse pregnancy outcomes in an at-risk population and to describe the relationship among aD1, antiphosphatidylserine-prothrombin, lupus anticoagulant, and other antiphospholipid antibodies (aPL).
Methods: Data were obtained from a prospective cohort of pregnant patients with aPL, with systemic lupus erythematosus (SLE) (n=59) or without SLE (n=106), or SLE without aPL (n=100) (PROMISSE [Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus and Antiphospholipid Syndrome] study; NCT00198068). Levels of aD1 and antiphosphatidylserine-prothrombin were quantified with the QUANTA Flash and QUANTA Lite systems, respectively, in sera collected at less than 18 weeks of gestation.
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