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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2121-2126.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-07-2422.
Submitted July 17, 2003
Accepted November 7, 2003
Antibodies to tissue-type plasminogen activator (tPA) in patients with antiphospholipid syndrome: evidence of interaction between the antibodies and the catalytic domain of tPA in two patients
Massimo Cugno*, Mara Cabibbe, Monica Galli, Pier Luigi Meroni, Sonia Caccia, Rosaria Russo, Bianca Bottasso, and Pier Mannuccio Mannucci
Department of Internal Medicine, University of Milan, Milan, Italy; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy
Department of Hematology, Ospedali Riuniti, Bergamo, Italy
Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Biomedical Sciences and Technologies, University of Milan, Milan, Italy
* Corresponding author; email: massimo.cugno{at}unimi.it.
The causes of thrombosis and pregnancy loss in antiphospholipid syndrome (APS) are still unknown, although several hypotheses have been proposed and hypofibrinolysis has been implicated. Anti-tissue-type plasminogen activator (tPA) antibodies may induce fibrinolytic defects and preliminary data indicate an association with thrombosis in APS. We measured plasma anti-tPA antibody levels in 91 consecutive APS patients, 91 normal controls, 40 patients with antiphospholipid antibodies without APS symptoms and 23 patients with systemic lupus erythematosus (SLE) without antiphospholipid antibodies and APS symptoms. APS patients had anti-tPA antibody levels higher than controls (p=0.0001), SLE patients (p=0.0001) and asymptomatic antiphospholipid patients (p=0.05). A subgroup of 53 patients had plasma levels of tPA antigen higher (p=0.0001) and tPA activity lower (p=0.05) than controls, with an inverse correlation (r=-0.454, p=0.003) between anti-tPA antibody levels and tPA activity and no correlation with tPA antigen. The two patients with the highest antibody levels had tPA activity below the normal range. Their antibodies were respectively IgG1 and IgG3; both recognized human tPA, recombinant tPA and the catalytic domain of tPA, but not  2-glycoprotein-I, prothrombin, or plasminogen. Our data indicate that anti-tPA antibodies specifically interacting with the catalytic domain of tPA can be found in patients with APS, representing a possible cause of hypofibrinolysis.
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