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 2 patients

被引:56
作者
Cugno, M
Cabibbe, M
Galli, M
Meroni, PL
Caccia, S
Russo, R
Bottasso, B
Mannucci, PM
机构
[1] Univ Milan, Dept Internal Med, IRCCS, Ist Auxologico Italiano, I-20122 Milan, Italy
[2] Maggiore Hosp, IRCCS, Dept Internal Med, Milan, Italy
[3] Maggiore Hosp, IRCCS, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy
[4] Univ Milan, Milan, Italy
[5] Osped Riuniti Bergamo, Dept Hematol, I-24100 Bergamo, Italy
[6] Univ Milan, Dept Biomed Sci & Technol, I-20133 Milan, Italy
关键词
D O I
10.1182/blood-2003-07-2422
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The causes of thrombosis and pregnancy loss in anti phospholipid 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 patients with APS, 91 healthy controls, 40 patients with antiphospholipid antibodies without APS symptoms, and 23 patients with systemic lupus erythematosus (SLE) without antiphospholipid antibodies and APS symptoms. Patients with APS had anti-tPA antibody levels higher than controls (P = .0001), patients with SLE (P = .0001), and asymptomatic antiphospholipid patients (P = .05). A subgroup of 53 patients had plasma levels of tPA antigen higher (P = .0001) and tPA activity lower (P = .05) than controls, with an inverse correlation (r = -0.454; P = .003) between anti-tPA antibody levels and tPA activity and no correlation with tPA antigen. The 2 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 beta(2)-glycoprotein 1, 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. (C) 2004 by The American Society of Hematology.
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页码:2121 / 2126
页数:6
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