Antiphospholipid Syndrome

You have full text access to this OnlineOpen article

Beta2-glycoprotein I protects thrombin from inhibition by heparin cofactor II: Potentiation of this effect in the presence of anti–β2-glycoprotein I autoantibodies

  1. Soheila Rahgozar1,
  2. Bill Giannakopoulos1,
  3. Xiaokai Yan1,
  4. Jiewei Wei1,
  5. Jian Cheng Qi1,
  6. Rosalie Gemmell2,
  7. Steven A. Krilis1,*

Article first published online: 27 MAR 2008

DOI: 10.1002/art.23387

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 58, Issue 4, pages 1146–1155, April 2008

Additional Information

How to Cite

Rahgozar, S., Giannakopoulos, B., Yan, X., Wei, J., Cheng Qi, J., Gemmell, R. and Krilis, S. A. (2008), Beta2-glycoprotein I protects thrombin from inhibition by heparin cofactor II: Potentiation of this effect in the presence of anti–β2-glycoprotein I autoantibodies. Arthritis & Rheumatism, 58: 1146–1155. doi: 10.1002/art.23387

Author Information

  1. 1

    University of New South Wales, Sydney, New South Wales, Australia

  2. 2

    South Eastern Area Laboratory Serices Kogarah, St. George Hospital, Sydney, New South Wales, Australia

*Department of Immunology, Allergy and Infectious Diseases, University of New South Wales, St. George Hospital, 2 South Street, Sydney, New South Wales 2217, Australia

Publication History

  1. Issue published online: 27 MAR 2008
  2. Article first published online: 27 MAR 2008
  3. Manuscript Accepted: 20 DEC 2007
  4. Manuscript Received: 30 APR 2007

Funded by

  • National Health and Medical Research Council of Australia
  • Postgraduate scholarship from the National Health and Medical Research Council of Australia

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (261K)

Abstract

Objective

Beta2-glycoprotein I (β2GPI) is an important autoantigen in the antiphospholipid syndrome (APS). In vitro studies suggest that it may have multifaceted physiologic functions, since it displays both anticoagulant and procoagulant properties. We have previously reported that β2GPI can directly bind thrombin, a key serine protease in the coagulation pathway. The present study was undertaken to examine the influence of β2GPI on thrombin inactivation by the serpin heparin cofactor II (HCII). The effect of anti-β2GPI antibodies was also examined.

Methods

HCII inactivation of thrombin was assessed using chromogenic and various platelet functional assays. The influence of intact and proteolytically cleaved β2GPI and anti-β2GPI antibodies was determined in these systems.

Results

β2GPI protected thrombin against inactivation by HCII/heparin. Cleavage of β2GPI at Lys317–Thr318 abrogated its protective effect. Patient polyclonal IgG and murine monoclonal anti-β2GPI antibodies potentiated the procoagulant influence of β2GPI in this system.

Conclusion

These novel findings suggest that β2GPI may regulate thrombin inactivation by HCII/heparin. The observation that anti-β2GPI antibodies potentiate the protective effect of β2GPI on thrombin in this system, thereby promoting a procoagulant response, may potentially delineate one of the pathophysiologic mechanisms contributing to the prothrombotic tendency in patients with APS.

View Full Article (HTML) Get PDF (261K)