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

Massimo Cugno, Mara Cabibbe, Monica Galli, Pier Luigi Meroni, Sonia Caccia, Rosaria Russo, Biarca Bottasso, Pier Mannuccio Mannucci

Research output: Contribution to journalArticle

Abstract

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 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 β 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.

Original languageEnglish
Pages (from-to)2121-2126
Number of pages6
JournalBlood
Volume103
Issue number6
DOIs
Publication statusPublished - Mar 15 2004

ASJC Scopus subject areas

  • Hematology

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