Summary
Antiphospholipid syndrome is a disorder of recurrent thrombosis and pregnancy losses
associated with production of anticardiolipin antibodies and lupus anticoagulant positivity.
Recently, we have adapted a mouse model of induced venous thrombosis to study the
role of autoantibodies in thrombus formation. To determine whether immunoglobulins
from patients with the antiphospholipid syndrome play a role in thrombosis, we injected
groups of CDI mice either with immunoglobulins purified from seven patients with the
antiphospholipid syndrome (nine preparations studied: four IgG, three IgM and two
IgA) or with immunoglobulins of the same isotype from healthy controls. Seventy- two
h after injection, a non-occlusive thrombus was induced in the femoral veins of experimental
mice by a pinch injury; the thrombus areas as well as times of formation and disappearance
of the thrombi were measured. Eight of the nine antiphospholipid syndrome immunoglobulin
preparations caused a significant increase in mean thrombus area and a significant
delay in mean thrombus disappearance time as compared with normal controls. To determine
whether anticardiolipin antibodies might be involved, separate groups of mice were
injected with affinity-purified IgG (n = 2) or IgM (n = 2) anticardiolipin antibodies
or with normal immunoglobulins of the same isotype, and the effects on thrombus formation
compared. Mean thrombus area and mean disappearance times were again significantly
increased in all four groups injected with affinity-purified antibodies. This is the
first study to show that anticardiolipin antibodies of IgG, IgM and IgA isotypes may
play a role in thrombosis in vivo.
