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This Article Full Text Full Text (PDF) 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 Jacquemin, M. G. Articles by Saint-Remy, J.-M. R. Search for Related Content PubMed PubMed Citation Articles by Jacquemin, M. G. Articles by Saint-Remy, J.-M. R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Mechanism and Kinetics of Factor VIII Inactivation: Study With an IgG4 Monoclonal Antibody Derived From a Hemophilia A Patient With Inhibitor Marc G. Jacquemin, Benoît G. Desqueper, Abdellah Benhida, Luc Vander Elst, Marc F. Hoylaerts, Marleen Bakkus, Kris Thielemans, Jef Arnout, Kathelijne Peerlinck, Jean Guy G. Gilles, Jos Vermylen, and Jean-Marie R. Saint-Remy From the Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium; and the Department of Hematology-Immunology, Vrije Universiteit Brussels, Brussels, Belgium. The development of an immune response towards factor VIII (fVIII) remains a major complication for hemophilia A patients receiving fVIII infusions. The design of a specific therapy to restore unresponsiveness to fVIII has been hampered by the diversity of the anti-fVIII antibody. Molecular analysis of the specific immune response is therefore required. To this end, we have characterized an fVIII-specific human IgG4 monoclonal antibody (BO2C11) produced by a cell line derived from the memory B-cell repertoire of a hemophilia A patient with inhibitor. BO2C11 recognizes the C2 domain of fVIII and inhibits its binding to both von Willebrand factor (vWF) and phospholipids. It completely inhibits the procoagulant activity of native and activated fVIII, with a specific activity of approximately 7,000 Bethesda units/mg. vWF reduces the rate of fVIII inactivation by BO2C11. The antibody-fVIII association rate constant (kass ~7.4 × 105 M1 s1) is eightfold lower than that for vWF-fVIII association, whereas its dissociation rate constant (kdiss 1 × 105 s1) is 100-fold lower than that for the vWF-fVIII complex, which suggests that BO2C11 almost irreversibly neutralizes fVIII after its dissociation from vWF. BO2C11 is the first human monoclonal anti-fVIII IgG antibody that has been isolated and allows the study of fVIII inactivation at the molecular level. Blood, Vol. 92 No. 2 (July 15), 1998: pp. 496-506 © 1998 by the American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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