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Thromb Haemost 1999; 81(05): 748-757
DOI: 10.1055/s-0037-1614566
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Schattauer GmbH

Enhancement of Protein S Anticoagulant Function by β2-glycoprotein I, a Major Target Antigen of Antiphospholipid Antibodies:

β2-glycoprotein I Interferes with Binding of Protein S to Its Plasma Inhibitor, C4b-binding Protein
Joan T. Merrill
1   From the Division of Rheumatology, St. Luke’s/Roosevelt Hospital Center, New York, NY
,
Hong Wei Zhang
1   From the Division of Rheumatology, St. Luke’s/Roosevelt Hospital Center, New York, NY
,
Christine Shen
1   From the Division of Rheumatology, St. Luke’s/Roosevelt Hospital Center, New York, NY
,
Bryan T. Butman
2   PerImmune Inc., Rockville, MD
,
Eddie P. Jeffries
2   PerImmune Inc., Rockville, MD
,
Robert G. Lahita
1   From the Division of Rheumatology, St. Luke’s/Roosevelt Hospital Center, New York, NY
,
Barry L. Myones
3   Baylor College of Medicine, Houston, TX, USA
› Author Affiliations
Further Information

Publication History

Received 15 December 1997

Accepted after resubmission 20 January 1999

Publication Date:
09 December 2017 (online)

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Summary

Thrombosis in the antiphospholipid syndrome has been associated with acquired deficiency of the anticoagulant protein S. We sought evidence that β2-glycoprotein I, a major target antigen for antiphospholipid antibodies, is involved in regulation of protein S activity. Incubation of purified protein S or plasma with β2-glycoprotein I reversed functional modulation of protein S by its plasma inhibitor, the C4b-binding protein. In a plasma-free ELISA, β2-glycoprotein I prevented the binding of protein S and C4b-binding protein when pre-incubated with immobilized protein S but not when similarly preincu-bated with C4b-binding protein. β2-glycoprotein I in fluid phase interfered with precipitation of protein S by sepharose-bound C4b-binding protein. Effects of β2-glycoprotein I on protein S function were inhibited by one of four monoclonal anti-β2-glycoprotein I antibodies. These data suggest that β2-glycoprotein I helps maintain adequate plasma levels of circulating free, active protein S. Antiphospholipid (anti-β2-glycoprotein I) antibodies might cause sporadic thrombosis, at least in part, by impairing this novel regulatory mechanism.

 

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