Antibodies to fibrin-bound tissue-type plasminogen activator in systemic lupus erythematosus are associated with Raynaud's phenomenon and thrombosis.
Fibrinolysis triggered by t-PA bound to fibrin is one of the main antithrombotic 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 present study, 43 patients with SLE fulfilling the ACR criteria for the disease, 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 fibrin prepared as previously described (Anal Biochem 1986; 153; 201-210). Sera diluted 1:50 were incubated with fibrin-bound t-PA, the plates were then washed, and bound immunoglobulins were detected using a polyvalent peroxidase-labeled goat anti-human Ig. Plates coated with fibrin alone were used as controls. Sera were considered positive when A490/630 obtained with normal human sera in two independent test was greater than the mean plus 2 SD. Eleven of 43 (26%) SLE sera demonstrated antibody reactivity against fibrin-bound t-PA. Within the anti-t-PA positive group there was a higher proportion of SLE patients with severe Raynaud's phenomenon and thrombotic events when compared to the anti-t-PA 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.
Salazar-Paramo
M
M
University of Guadalajara, Mexico.
Garcia de la Torre
I
I
Fritzler
M J
MJ
Loyau
S
S
Anglés-Cano
E
E
D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D008297:Male; D011928:Raynaud Disease / Q000209:etiology / Q000276:immunology*; D013927:Thrombosis / Q000209:etiology / Q000276:immunology*; D010959:Tissue Plasminogen Activator / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D005337:Fibrin; D010959:Tissue Plasminogen Activator