Antibodies to tissue-type plasminogen activator in plasma from patients with primary antiphospholipid syndrome.
A reduction in fibrinolysis has been described in association with thrombosis in the primary antiphospholipid syndrome (PAPS). In this study, we measured anti-tissue-type plasminogen activator (t-PA) antibodies and anti-fibrin-bound t-PA antibodies as possible causes of hypofibrinolysis in 39 patients with PAPS. We also evaluated the differences in anti t-PA antibodies between patients without previous thrombosis (20 patients) and patients with previous episodes of thrombosis (19 patients: deep vein thrombosis in nine, ischaemic stroke in six, arterial leg thrombosis in one, hepatic vein thrombosis in one, thrombophlebitis in one and cerebral venous thrombosis in one). Anti-t-PA antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and anti-t-PA fibrin-bound antibodies were measured by a solid-phase fibrin immunoassay (SOFIA) in 39 patients with PAPS and in 39 controls matched for gender and age. High levels of IgG anti-t-PA were found in three out of 39 patients with PAPS, and all three patients had a history of thrombosis; four other patients, one of whom had a history of thrombotic events, had high titres of antibodies directed against fibrin-bound t-PA. In addition, patients with ischaemic stroke had significantly higher levels of IgG anti-t-PA than patients without thrombosis (P = 0.029). In conclusion, our data showed that, in patients with PAPS, the highest levels of anti-t-PA antibodies were present in subjects with previous thrombotic events. The discrepancy in the results obtained with two methods of detection of anti-t-PA antibodies, ELISA and SOFIA, indicates a different interaction of the antibodies with the t-PA molecules, which are directly bound to polystyrene plates in ELISA and bound to fibrin as a bridging molecule in SOFIA.
Cugno
M
M
Department of Internal Medicine, IRCCS Maggiore Hospital, University of Milan, Milan, Italy. massimo.cugno.unimi.it
Dominguez
M
M
Cabibbe
M
M
Bisiani
G
G
Galli
M
M
Angles-Cano
E
E
Agostoni
A
A
D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D013927:Thrombosis / Q000209:etiology / Q000276:immunology*; D010959:Tissue Plasminogen Activator / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D010959:Tissue Plasminogen Activator