β2-glycoprotein I is necessary to inhibit protein C activity by monoclonal anticardiolipin antibodies

Masahiro Ieko, Kenji Ichikawa, Douglas A. Triplett, Eiji Matsuura, Tatsuya Atsumi, Ken Ichi Sawada, Takao Koike

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Objective. To clarify mechanisms of the thrombosis associated with anticardiolipin antibodies (aCL), we examined the effects on activated protein C (APC) of monoclonal aCL and β2-glycoprotein I (β2GPI), which is required for formation of the epitopes of aCL. Methods. We developed the chromogenic assay, in which the degradation of coagulation factor Va by APC is reflected in the reduced generation of thrombin from prothrombin, using soybean trypsin inhibitor to inhibit APC. APC activities were measured in the presence and absence of 3.4 μM β2GPI and/or 2.5 μg/ml of IgM monoclonal aCL (EY2C9 and EY1C8) established from peripheral blood lymphocytes obtained from a patient with aCL. Results. Without APC, the formed thrombin activity decreased by the addition of 3.4 μM β2GPI. When 12.8 nM APC was added, β2GPI partially reversed the APC-induced inhibition of thrombin generation in a concentration-dependent manner. With 3.4 μM β2GPI, the thrombin generation in monoclonal aCL (2.5 μg/ml) decreased to 77.1-80.2% by the addition of 12.8 nM APC, but the values were above that in the control IgM (72.7%). Without β2GPI, the APC activity was unaffected by the addition of monoclonal aCL. Conclusion. Beta2-glycoprotein I exhibits procoagulant activity by inhibiting APC activity and anticoagulant activity by inhibiting thrombin generation. Any further inhibition of APC activity was caused by monoclonal aCL and only in the presence of β2GPI.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalArthritis and Rheumatism
Volume42
Issue number1
DOIs
Publication statusPublished - Jan 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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