title: beta 2 glycoprotein-I inhibits factor XII activation on triglyceride rich lipoproteins: the effect of antibodies from plasma of patients with antiphospholipid syndrome.
abstract: It is now well recognised that antiphospholipid antibodies are associated with thrombosis and recurrent fetal loss. Some antiphospholipid antibodies (aPAs) have been shown to require a cofactor, beta 2 glycoprotein-I (beta 2 GPI), for binding to phospholipids, and recently beta 2 GPI has been identified as the antigenic target for some aPAs. beta 2 GPI possesses in vitro anticoagulant properties and modulation of beta 2 GPI function may therefore result in altered haemostatic regulation. In the present study, the influence of plasma derived aPAs and beta 2 GPI on factor XII activation on the surface of very low density lipoprotein (VLDL) was investigated. Factor XIIa generation was dependent on lipoprotein lipase treatment of VLDL and beta 2 GPI inhibited the factor XIIa generation in a concentration dependent manner. No consistent effects on factor XIIa generation were demonstrated with the IgG fractions from patients with aPAs. Inhibition of the beta 2 GPI activity was demonstrated by some antibodies, and study with cardiolipin affinity purified antibody indicated that antibody concentration is critical. These results suggest that perturbation of beta 2 GPI function may contribute to the pathogenic mechanism for thrombosis in some patients with aPAs.
authors.affiliation: Department of Haematology, University College London Medical School, UK.
authors.forename: T
authors.initials: T
authors.lastname: McNally
authors.forename: I J
authors.initials: IJ
authors.lastname: Mackie
authors.forename: D A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: S J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D017153:Antibodies, Anticardiolipin / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000097:blood*; D016022:Case-Control Studies; D015956:Factor XIIa / Q000096:biosynthesis*; D005260:Female; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood*; D053482:beta 2-Glycoprotein I
chemical_list: D000906:Antibodies; D017153:Antibodies, Anticardiolipin; D006023:Glycoproteins; D007074:Immunoglobulin G; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D053482:beta 2-Glycoprotein I; D015956:Factor XIIa