Effects of β2‐glycoprotein I and monoclonal anticardiolipin antibodies in platelet interaction with subendothelium under flow conditions

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Abstract
Objective To evaluate whether the effect of human monoclonal anticardiolipin antibodies (aCL) on platelet interaction with the subendothelium under flow conditions is dependent on β2‐glycoprotein I (β2GPI). Methods Three monoclonal IgM aCL with anti‐β2GPI activity (TM1B3, GR1D5, and EY2C9) obtained from patients with antiphospholipid syndrome, a monoclonal aCL with lupus anticoagulant activity but without anti‐β2GPI activity (FRO) obtained from a patient with a splenic lymphoma, and a control monoclonal IgM without aCL activity were used. TM1B3, GR1D5, EY2C9, FRO, and control IgM (30 μg/ml) were added to reconstituted blood containing gel‐filtered platelets (200 × 109/liter), factor VIII (100 units/dl), and fibrinogen (1.5 gm/liter). Samples were perfused (wall‐shear rate 800 seconds−1), with and without the addition of purified β2GPI (20 μg/ml), through annular chambers containing collagen‐rich denuded vascular segments, and the percentages of surface covered by platelets and by thrombi were evaluated. Results No differences in the percentages of surface covered by platelets and by thrombi were observed among samples with TM1B3, GR1D5, EY2C9, FRO, and control IgM added when reconstituted blood samples without β2GPI were used. However, a significant increase in the percentage of surface covered by platelets was observed in the presence of TM1B3, GR1D5, and EY2C9 but not in the presence of FRO when samples containing β2GPI were used. Increased thrombi formation was induced by TM1B3 and GR1D5 but not by EY2C9 or FRO in samples with added β2GPI. Conclusion Monoclonal aCL require anti‐β2GPI activity to promote platelet interaction with the subendothelium under flow conditions.
Funding Information
  • Fondo de Investigación Sanitaria (99/0148, 00/1048)
  • Arthritis and Rheumatism Council
  • LUPUS UK
  • Generalitat de Catalunya (FI-00684)