Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies in platelet interaction with subendothelium under flow conditions.
OBJECTIVE
To evaluate whether the effect of human monoclonal anticardiolipin antibodies (aCL) on platelet interaction with the subendothelium under flow conditions is dependent on beta(2)-glycoprotein I (beta(2)GPI).


METHODS
Three monoclonal IgM aCL with anti-beta(2)GPI activity (TM1B3, GR1D5, and EY2C9) obtained from patients with antiphospholipid syndrome, a monoclonal aCL with lupus anticoagulant activity but without anti-beta(2)GPI 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 microg/ml) were added to reconstituted blood containing gel-filtered platelets (200 x 10(9)/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 beta(2)GPI (20 microg/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 beta(2)GPI 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 beta(2)GPI were used. Increased thrombi formation was induced by TM1B3 and GR1D5 but not by EY2C9 or FRO in samples with added beta(2)GPI.


CONCLUSIONS
Monoclonal aCL require anti-beta(2)GPI activity to promote platelet interaction with the subendothelium under flow conditions.
Font
Josep
J
Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Espinosa
Gerard
G
Tàssies
Dolors
D
Pino
Marc
M
Khamashta
Munther A
MA
Gallart
Teresa
T
Cervera
Ricard
R
Escolar
Ginés
G
Hughes
Graham R V
GR
Ingelmo
Miguel
M
Ordinas
Antoni
A
Reverter
Joan-Carles
JC
D017153:Antibodies, Anticardiolipin / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D007075:Immunoglobulin M; D053482:beta 2-Glycoprotein I