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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   *
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
,
Mary L. Pound
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
,
Zuowei Su
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
,
G. Michael Iverson
2   La Jolla Pharmaceutical Company, San Diego, California, USA
,
Thomas L. Ortel
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
› Author AffiliationsThis work was supported by a grant-in-aid from the American Heart Association, Mid-Atlantic Affiliate (TLO), and a Midcareer Investigator Award in Patient-Oriented Research (K24 AIO1603-01) from the NIH (TLO). We thank Dr. Wayne F. Beyer, Department of Pathology, Duke University Medical Center, for amino acid sequencing and composition analyses of β2GPI, Mr. Keith F. Klemp for determination of patients’ genotypes, and Dr. Deborah A. Lewis for critically reviewing this manuscript.
Further Information

Publication History

Received 10 December 2001

Accepted after resubmission 03 June 2002

Publication Date:
09 December 2017 (online)

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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

* Present address: Division of Proteomics Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan


Presented in part at XVIIIth Congress of the International Society on Thrombosis and Haemostasis, Paris, France, July 6-12, 2001


 

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