β2 Glycoprotein-I Inhibits Factor XII Activation on Triglyceride Rich Lipoproteins: The Effect of Antibodies from Plasma of Patients with Antiphospholipid Syndrome

T McNally; I J Mackie; D A Isenberg; S J Machin

doi:10.1055/s-0038-1650558

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 76(02): 220-225
DOI: 10.1055/s-0038-1650558

Original Article

Schattauer GmbH Stuttgart

β₂ Glycoprotein-I Inhibits Factor XII Activation on Triglyceride Rich Lipoproteins: The Effect of Antibodies from Plasma of Patients with Antiphospholipid Syndrome

T McNally

The Department of Haematology, University College London Medical School London, UK

,

I J Mackie

The Department of Haematology, University College London Medical School London, UK

,

D A Isenberg

¹The Department of Rheumatology, University College London Medical School London, UK

,

S J Machin

The Department of Haematology, University College London Medical School London, UK

› Author Affiliations

Abstract

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Summary

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, β₂ glyco-protein-I (β₂GPI), for binding to phospholipids, and recently β₂GPI has been identified as the antigenic target for some aPAs. β₂GPI possesses in vitro anticoagulant properties and modulation of β₂GPI function may therefore result in altered haemostatic regulation. In the present study, the influence of plasma derived aPAs and β₂GPI 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 β₂GPI 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 β₂GPI 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 β₂GPI function may contribute to the pathogenic mechanism for thrombosis in some patients with aPAs. .

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References

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