Anti-β2-glycoprotein I Antibody-mediated Inhibition of Activated Protein C Requires Binding of β2-glycoprotein I to Phospholipids

Tomonori Izumi; Mary L. Pound; Zuowei Su; G. Michael Iverson; Thomas L. Ortel

doi:10.1055/s-0037-1613265

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(04): 620-626
DOI: 10.1055/s-0037-1613265

Review Article

Schattauer GmbH

Anti-β₂-glycoprotein I Antibody-mediated Inhibition of Activated Protein C Requires Binding of β₂-glycoprotein I to Phospholipids

Tomonori Izumi^*

¹Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA

,

Mary L. Pound

¹Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA

,

Zuowei Su

¹Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA

,

G. Michael Iverson

²La Jolla Pharmaceutical Company, San Diego, California, USA

,

Thomas L. Ortel

¹Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA

› Author Affiliations

Abstract

Summary

To clarify the role(s) of anti-β₂GPI antibodies on thrombosis in antiphospholipid antibody syndromes (APS), the effect of IgG from three patients on activated protein C (APC) was investigated using phospholipid vesicles and purified proteins. Two of the total IgG inhibited APC activity in the presence of β₂GPI, whereas the third IgG did not. In addition, one IgG inhibited APC activity without β₂GPI. Anti-β₂GPI IgG from the two inhibitory IgG preparations inhibited APC activity only in the presence of β₂GPI. Inhibition was suppressed partially by excess APC and almost completely by excess phospholipid vesicles. Cleaved β₂GPI, a non-phospholipid-binding form, did not support inhibitory activity, even though the anti-β₂GPI IgG bound to the cleaved molecule. This study confirms that anti-β₂GPI antibodies from APS patients inhibit APC activity, and demonstrates the requirement of phospholipid binding of β₂GPI for expression of the inhibitory activity of these antibodies.

Keywords

Antiphospholipid antibody syndrome - β₂-glycoprotein I - apolipoprotein H - activated protein C - phospholipid binding

Full Text

References

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