ANTIBODIES TO FIBRIN-BOUND TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN SYSTEMIC LUPUS-ERYTHEMATOSUS ARE ASSOCIATED WITH RAYNAUDS-PHENOMENON AND THROMBOSIS

Fibrinolysis triggered by t-PA bound to fibrin is one of the main anti thrombotic mechanisms. Defects in the fibrinolytic system - decreased tissue-type plasminogen activator (t-PA) activity and elevated levels of plasminogen activator inhibitor (PAI-1), in patients with SLE have been associated with an increased tendency to thrombosis. In the prese nt study, 43 patients with SLE fulfilling the ACR criteria for the dis ease, were studied for the presence of autoantibodies to fibrin-bound t-PA, i.e. the physiological active form of this plasminogen activator . A solution of 200 IU/ml of t-PA was incubated with solid-phase fibri n prepared as previously described (Anal Biochem 1986; 153: 201-210). Sera diluted 1:50 were incubated with fibrin-bound t-PA, the plates we re then washed, and bound immunoglobulins were detected using a polyva lent peroxidase-labeled goat anti-human Ig. Plates coated with fibrin alone were used as controls. Sera were considered positive when A490/6 30 obtained with normal human sera in two independent test was greater than the mean plus 2 SD. Eleven of 43 (26%) SLE sera demonstrated ant ibody reactivity against fibrin-bound t-PA. Within the anti-t-PA posit ive group there was a higher proportion of SLE patients with severe Ra ynaud's phenomenon and thrombotic events when compared to the anti-t-P A negative group: 36% vs 6% and 18% vs 6%, respectively. These results suggest that autoantibodies to fibrin-bound t-PA could play a role in the pathogenesis of vascular disease in some SLE patients.