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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2422v1 103/6/2121    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cugno, M. Articles by Mannucci, P. M. Search for Related Content PubMed PubMed Citation Articles by Cugno, M. Articles by Mannucci, P. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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, Bianca Bottasso, and Pier Mannuccio Mannucci From the Department of Internal Medicine and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milan, Milan, Italy; Department of Hematology, Ospedali Riuniti, Bergamo, Italy; Department of Internal Medicine, University of Milan, Istituto Auxologico Italiano IRCCS, Milan, Italy; and Department of Biomedical Sciences and Technologies, University of Milan, Milan, Italy. 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 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X.-X. Chen, Y.-Y. Gu, S.-J. Li, J. Qian, K.-K. Hwang, P. P. Chen, S.-L. Chen, and C.-D. Yang Some Plasmin-Induced Antibodies Bind to Cardiolipin, Display Lupus Anticoagulant Activity and Induce Fetal Loss in Mice J. Immunol., April 15, 2007; 178(8): 5351 - 5356. [Abstract] [Full Text] [PDF] B. Giannakopoulos, F. Passam, S. Rahgozar, and S. A. Krilis Current concepts on the pathogenesis of the antiphospholipid syndrome Blood, January 15, 2007; 109(2): 422 - 430. [Abstract] [Full Text] [PDF] M. Rieger, P. M. Mannucci, J. A. K. Hovinga, A. Herzog, G. Gerstenbauer, C. Konetschny, K. Zimmermann, I. Scharrer, F. Peyvandi, M. Galbusera, et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases Blood, August 15, 2005; 106(4): 1262 - 1267. [Abstract] [Full Text] [PDF]

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