ROLE OF ANTIPHOSPHOLIPID ANTIBODIES IN THE PATHOGENESIS OF THROMBOSIS IN ANTIPHOSPHOLIPID SYNDROME

The role of antiphospholipid antibodies in the pathogenesis of thrombosis frequently encountered in patients with antiphospholipid syndrome was studied. Anticardiolipin antibody (ACA), detected by enzyme-linked immunosorbent assay (ELISA), and lupus anticoagulant (LA) activity were measured in patients with systemic lupus erythematosus (SLE), pulmonary embolism (PE), and Kawasaki disease (KD). ACA was often elevated in all three disorders, but LA was detected only in SLE. No LA activity was detected in PE and KD in spite of high titer of ACA. In addition, LA activity, irrespective of the level of ACA, appeared to be associated with thrombotic episodes in SLE. An IgG fraction obtained from a patient with SLE having both ACA and LA inhibited thrombomodulin-dependent activation of protein C by thrombin or factor Xa, while IgG from a patient with KD showing high titer of ACA did not. Similar results were obtained in experiments using two different monoclonal antibodies against cardiolipin. Our results suggest that LA is a predisposing factor for thrombosis partly because it inhibits thrombomodulin-dependent activation of protein C.