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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-05-1310. This Article Full Text (PDF) All Versions of this Article: 2002-05-1310v1 101/1/157    most recent Alert me when this article is cited Alert me if a correction is posted 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 Jankowski, M. Articles by Arnout, J. Search for Related Content PubMed PubMed Citation Articles by Jankowski, M. Articles by Arnout, J. Social Bookmarking                   What's this? Submitted May 6, 2002 Accepted July 11, 2002 Thrombogenicity of ß2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically-induced thrombosis model in the hamster Milosz Jankowski, Ingrid Vreys, Christine Wittevrongel, Doris Boon, Jos Vermylen, Marc F Hoylaerts, and Jef Arnout* Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium * Corresponding author; email: jef.arnout{at}med.kuleuven.ac.be. We previously showed that ß2GPI-dependent lupus anticoagulants (LA) form bivalent antigen-antibody complexes with high affinity for phospholipids; these complexes are responsible for their in vitro anticoagulant effect. We now studied the role of these bivalent complexes in arterial thrombosis in the hamster. Three monoclonal antibodies (Mab) raised against human ß2GPI were selected on the basis of their cross-reactivity with hamster ß2GPI. Two of these, one with LA activity (5H2) and one with only anticardiolipin properties (11E8), were infused at 0 to 10 mg/kg prior to photochemically-induced vessel damage. 5H2 promoted thrombus formation dose-dependently, raising the thrombus size from 6.0 arbitrary units (AU) in controls (n=9) to 65.0 AU in the high dose group (10 mg/kg, n=6, p=0.007). The LA negative Mab 11E8 and Mab 27A8, reactive with human ß2GPI exclusively, did not significantly promote thrombus formation. In a second set of experiments, intact Mab 5H2 was compared to its fragments. Intact Mab 5H2 at 3.3 mg/kg and the equimolar dose of F(ab')2 fragments (2.2 mg/kg), promoted thrombus formation equally well (55.8 AU, n=8 and 62.5 AU, n=7 respectively); Mab 5H2 derived Fab' fragments were inactive. Immunohistochemical analysis showed platelet-rich thrombi, with 5H2 or its F(ab')2 fragments mainly bound to individual platelets. Our results indicate that bivalent immune complex formation plays an important role in the genesis of arterial thrombosis by certain aPL. Cellular activation via the Fc portion of these immune complexes however is not essential, since F(ab')2 fragments of 5H2 still promote thrombus formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Romay-Penabad, M. G. Montiel-Manzano, T. Shilagard, E. Papalardo, G. Vargas, A. B. Deora, M. Wang, A. T. Jacovina, E. Garcia-Latorre, E. Reyes-Maldonado, et al. Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo Blood, October 1, 2009; 114(14): 3074 - 3083. [Abstract] [Full Text] [PDF] S. V. Seshan, C.-W. Franzke, P. Redecha, M. Monestier, N. Mackman, and G. 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