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Blood, 15 January 2007, Vol. 109, No. 2, pp. 610-612. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-05-022756. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-05-022756v1 109/2/610    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 Dasgupta, S. Articles by Lacroix-Desmazes, S. Search for Related Content PubMed PubMed Citation Articles by Dasgupta, S. Articles by Lacroix-Desmazes, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 11, 2006 Accepted September 4, 2006 VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors Suryasarathi Dasgupta, Yohann Repesse, Jagadeesh Bayry, Ana-Maria Navarrete, Bharath Wootla, Sandrine Delignat, Theano Irinopoulou, Caroline Kamate, Jean-Marie Saint-Remy, Marc Jacquemin, Peter J Lenting, Annie Borel-Derlon, Srinivas V Kaveri, and Sebastien Lacroix-Desmazes* INSERM U681, Paris, France Universite de Caen, Laboratoire d'hematologie, Caen, France Institut du Fer a Moulin, Paris, France Laboratory for Thrombosis and Haemostasis, University Medical Center, Utrecht, The Netherlands Center for Molecular and Vascular Biology, Katolische Universtitat Leuven, Belgium * Corresponding author; email: sebastien.lacroix-desmazes{at}umrs681.jussieu.fr. Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in patients with hemophilia A has been evoked, but lacks clear cellular and molecular rational. Here, we demonstrate that VWF protects FVIII from being endocytosed by human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells. The immunoprotective effect of VWF requires a physical interaction with FVIII, as the endocytosis of FVIII was significantly restored upon hindering the formation of the VWF-FVIII complex. Interestingly, VWF had no direct inhibitory effect either on the ability of DCs to present antigenic peptides, or on the activation potency of CD4+ T cells. We thus propose that VWF may reduce the immunogenicity of FVIII by preventing, upstream from the activation of immune effectors, the entry of FVIII in professional antigen presenting cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Qadura, B. Waters, E. Burnett, R. Chegeni, S. Bradshaw, C. Hough, M. Othman, and D. Lillicrap Recombinant and plasma-derived factor VIII products induce distinct splenic cytokine microenvironments in hemophilia A mice Blood, July 23, 2009; 114(4): 871 - 880. [Abstract] [Full Text] [PDF] M. van den Biggelaar, E. A.M. Bouwens, N. A. Kootstra, R. P. Hebbel, J. Voorberg, and K. Mertens Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells Haematologica, May 1, 2009; 94(5): 670 - 678. [Abstract] [Full Text] [PDF] S. Dasgupta, J. Bayry, S. Andre, J. D. Dimitrov, S. V. Kaveri, and S. Lacroix-Desmazes Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins J. Immunol., August 1, 2008; 181(3): 1609 - 1615. [Abstract] [Full Text] [PDF] S. Lacroix-Desmazes, A.-M. Navarrete, S. Andre, J. Bayry, S. V. Kaveri, and S. Dasgupta Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A Blood, July 15, 2008; 112(2): 240 - 249. [Abstract] [Full Text] [PDF] S. Dasgupta, A. M. Navarrete, S. Andre, B. Wootla, S. Delignat, Y. Repesse, J. Bayry, A. Nicoletti, E. L. Saenko, R. d'Oiron, et al. Factor VIII bypasses CD91/LRP for endocytosis by dendritic cells leading to T-cell activation Haematologica, January 1, 2008; 93(1): 83 - 89. [Abstract] [Full Text] [PDF] S. Delignat, S. Dasgupta, S. Andre, A.-M. Navarrete, S. V. Kaveri, J. Bayry, M.-H. Andre, S. Chtourou, Z. Tellier, and S. Lacroix-Desmazes Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A Haematologica, October 1, 2007; 92(10): 1423 - 1426. [Abstract] [Full Text] [PDF] T. Calvez, Y. Laurian, and J. Goudemand Associations between type of product and inhibitors in previously untreated patients (PUPs) with severe hemophilia: switches and particular products can disturb analysis Blood, August 1, 2007; 110(3): 1073 - 1074. [Full Text] [PDF] S. Dasgupta, A.-M. Navarrete, J. Bayry, S. Delignat, B. Wootla, S. Andre, O. Christophe, M. Nascimbeni, M. Jacquemin, L. Martinez-Pomares, et al. A role for exposed mannosylations in presentation of human therapeutic self-proteins to CD4+ T lymphocytes PNAS, May 22, 2007; 104(21): 8965 - 8970. [Abstract] [Full Text] [PDF]

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