Premium
Suppressed intrinsic fibrinolytic activity by monoclonal anti‐beta‐2 glycoprotein I autoantibodies: possible mechanism for thrombosis in patients with antiphospholipid syndrome
Author(s) -
Takeuchi Rie,
Atsumi Tatsuya,
Ieko Masahiro,
Amasaki Yoshiharu,
Ichikawa Kenji,
Koike Takao
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03928.x
Subject(s) - fibrinolysis , coagulation , autoantibody , monoclonal antibody , antibody , epitope , antiphospholipid syndrome , endocrinology , immunology , medicine , factor xii , chemistry , microbiology and biotechnology , biology
Summary. β2‐glycoprotein I (β2GPI) bears the epitope(s) for autoimmune anticardiolipin antibodies (aCL) frequently present in patients with antiphospholipid syndrome (APS). β2GPI is involved in coagulation and fibrinolytic systems, including inhibition of contact activation. Coagulation factor XII is an initiator of intrinsic coagulation and also of intrinsic fibrinolysis. We investigated the effect of aCL (= anti‐β2GPI antibodies), regarding intrinsic fibrinolysis using autoimmune monoclonal anti‐β2GPI antibodies derived from a patient with APS or from an NZW/BXSB‐F1 mouse. We developed a chromogenic assay system to determine intrinsic fibrinolytic activity. The reaction was activated by kaolin in the euglobulin fraction. Exogenous β2GPI slightly suppressed intrinsic fibrinolytic activity of the euglobulin fraction from normal plasma. Human monoclonal anti‐β2GPI antibody (EY2C9) and mouse monoclonal anti‐β2GPI antibody (WBCAL‐1) in the presence of β2GPI decreased the activity. In this system, the suppression remained significant in the presence of an excess of exogenous activated factor XII. Euglobulin fractions from APS patients' plasma paralleled low activities of intrinsic fibrinolysis compared with those from healthy subjects. Our results suggest that β2GPI and anti‐β2GPI antibodies suppress intrinsic fibrinolytic activities. This suppression was not only due to inhibition of factor XII activation but was also related to function of activated factor XII (XIIa). These phenomena partly explain the mechanisms of thrombosis in APS.