Enhancement of protein S anticoagulant function by beta2-glycoprotein I, a major target antigen of antiphospholipid antibodies: beta2-glycoprotein I interferes with binding of protein S to its plasma inhibitor, C4b-binding protein

Thromb Haemost. 1999 May;81(5):748-57.


Thrombosis in the antiphospholipid syndrome has been associated with acquired deficiency of the anticoagulant protein S. We sought evidence that beta2-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 beta2-glycoprotein I reversed functional modulation of protein S by its plasma inhibitor, the C4b-binding protein. In a plasma-free ELISA, beta2-glycoprotein I prevented the binding of protein S and C4b-binding protein when preincubated with immobilized protein S but not when similarly preincubated with C4b-binding protein. beta2-glycoprotein I in fluid phase interfered with precipitation of protein S by sepharose-bound C4b-binding protein. Effects of beta2-glycoprotein I on protein S function were inhibited by one of four monoclonal anti-beta2-glycoprotein 1 antibodies. These data suggest that beta2-glycoprotein I helps maintain adequate plasma levels of circulating free, active protein S. Antiphospholipid (anti-beta2-glycoprotein I) antibodies might cause sporadic thrombosis, at least in part, by impairing this novel regulatory mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antiphospholipid / blood
  • Antibodies, Antiphospholipid / immunology
  • Blood Coagulation
  • Complement Inactivator Proteins*
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / immunology
  • Glycoproteins / metabolism*
  • Humans
  • Protein S / metabolism*
  • Receptors, Complement / blood*
  • Thrombosis / blood*
  • beta 2-Glycoprotein I


  • Antibodies, Antiphospholipid
  • Complement Inactivator Proteins
  • Glycoproteins
  • Protein S
  • Receptors, Complement
  • beta 2-Glycoprotein I