HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, C.-D. Articles by Chen, P. P. Search for Related Content PubMed PubMed Citation Articles by Yang, C.-D. Articles by Chen, P. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Identification of Anti-Plasmin Antibodies in the Antiphospholipid Syndrome That Inhibit Degradation of Fibrin¹

Cheng-De Yang^2,3,*, Kwan-Ki Hwang^2,4,*, Weihong Yan, Kerry Gallagher, John FitzGerald^*, Jennifer M. Grossman^*, Bevra H. Hahn^* and Pojen P. Chen^*

^* Department of Medicine, Division of Rheumatology; Department of Chemistry and Biochemistry; and Department of Pediatrics, University of California, Los Angeles, CA 90095

The combined presence of anti-phospholipid Ab (aPL) and thrombosis is recognized as the antiphospholipid syndrome (APS). The aPL represent a heterogeneous group of Ab that recognize various phospholipids (PL), PL-binding plasma proteins, and/or PL-protein complexes. Recently, we found the presence of antithrombin Ab in some APS patients and that some of these anti-thrombin Ab could inhibit thrombin inactivation by antithrombin. Considering that thrombin is homologous to plasmin, which dissolves fibrin, we hypothesize that some APS patients may have Ab that react with plasmin, and that some anti-plasmin Ab may interfere with the plasmin-mediated lysis of fibrin clots. To test this hypothesis, we searched for anti-plasmin Ab in APS patients and then studied those found for their effects on the fibrinolytic pathway. The results revealed that seven of 25 (28%) APS patients have IgG anti-plasmin Ab (using the mean OD plus 3 SD of 20 normal controls as the cutoff) and that six of six patient-derived IgG anti–thrombin mAb bind to plasmin with relative K_d values ranging from 5.6 x 10^–8 to 1 x 10^–6 M. These K_d values probably represent affinities in the higher ranges known for human IgG autoantibodies against protein autoantigens. Of these mAb, one could reduce the plasmin-mediated lysis of fibrin clots. These findings suggest that plasmin may be an important driving Ag for some aPL B cells in APS patients, and that the induced anti-plasmin Ab may act either directly, by binding to plasmin and inhibiting its fibrinolytic activity, or indirectly, by cross-reacting with other homologous proteins in the coagulation cascade to promote thrombosis.

This article has been cited by other articles:

				Y.-H. Yang, D. Chien, M. Wu, J. FitzGerald, J. M. Grossman, B. H. Hahn, K.-K. Hwang, and P. P. Chen Novel Autoantibodies against the Activated Coagulation Factor IX (FIXa) in the Antiphospholipid Syndrome That Interpose the FIXa Regulation by Antithrombin J. Immunol., February 1, 2009; 182(3): 1674 - 1680. [Abstract] [Full Text] [PDF]

				D. J. Bautz, G. A. Preston, S. Lionaki, P. Hewins, A. S. Wolberg, J. J. Yang, S. L. Hogan, H. Chin, S. Moll, J. C. Jennette, et al. Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2421 - 2429. [Abstract] [Full Text] [PDF]

				R Forastiero and M Martinuzzo Prothrombotic mechanisms based on the impairment of fibrinolysis in the antiphospholipid syndrome Lupus, October 1, 2008; 17(10): 872 - 877. [Abstract] [PDF]

				P. Chen, C. Yang, K Ede, C. Wu, J. FitzGerald, and J. Grossman Some antiphospholipid antibodies bind to hemostasis and fibrinolysis proteases and promote thrombosis Lupus, October 1, 2008; 17(10): 916 - 921. [Abstract] [PDF]

				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]

				S. M. Abo and V. A. DeBari Laboratory Evaluation of the Antiphospholipid Syndrome Ann. Clin. Lab. Sci., January 1, 2007; 37(1): 3 - 14. [Abstract] [Full Text] [PDF]

				Y.-H. Yang, K.-K. Hwang, J. FitzGerald, J. M. Grossman, M. Taylor, B. H. Hahn, and P. P. Chen Antibodies against the Activated Coagulation Factor X (FXa) in the Antiphospholipid Syndrome That Interfere with the FXa Inactivation by Antithrombin J. Immunol., December 1, 2006; 177(11): 8219 - 8225. [Abstract] [Full Text] [PDF]