beta 2 glycoprotein-I inhibits factor XII activation on triglyceride rich lipoproteins: the effect of antibodies from plasma of patients with antiphospholipid syndrome.
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.
McNally
T
T
Department of Haematology, University College London Medical School, UK.
Mackie
I J
IJ
Isenberg
D A
DA
Machin
S J
SJ
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
D000906:Antibodies; D017153:Antibodies, Anticardiolipin; D006023:Glycoproteins; D007074:Immunoglobulin G; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D053482:beta 2-Glycoprotein I; D015956:Factor XIIa