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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3415-3422. Prepublished online as a Blood First Edition Paper on August 9, 2005; DOI 10.1182/blood-2005-03-1182. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1182v1 106/10/3415    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 Hausl, C. Articles by Reipert, B. M. Search for Related Content PubMed PubMed Citation Articles by Hausl, C. Articles by Reipert, B. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY High-dose factor VIII inhibits factor VIII–specific memory B cells in hemophilia A with factor VIII inhibitors Christina Hausl, Rafi U. Ahmad, Maria Sasgary, Christopher B. Doering, Pete Lollar, Günter Richter, Hans Peter Schwarz, Peter L. Turecek, and Birgit M. Reipert From Biomolecular Therapeutics GmbH (BMT) Research, Vienna, Austria; Baxter BioScience, Vienna, Austria; and the American Family Life Assurance Company (AFLAC) Cancer Center and Blood Disorders Service, Children's Hospital of Atlanta, Atlanta, GA. Hemophilia A in its severe form is a life-threatening hemorrhagic disease that is caused by mutations in the factor VIII (FVIII) gene (symbol F8). About 25% of patients who receive replacement therapy develop neutralizing antibodies that inhibit the function of substituted FVIII. Long-term application of high doses of FVIII has evolved as an effective therapy to eradicate the antibodies and to induce long-lasting immune tolerance. Little is known, however, about the immunologic mechanisms that cause the down-modulation of anti-FVIII antibodies by high doses of FVIII. We report that high doses of FVIII inhibit the restimulation of FVIII-specific memory B cells and their differentiation into antibody-secreting plasma cells in vitro and in vivo in a murine model of hemophilia A. The inhibition of memory B-cell responses is irreversible and not mediated by FVIII-specific T cells. Furthermore, it seems to involve the activation of caspases. We conclude that the inhibition of FVIII-specific memory B cells might be an early event in the down-modulation of anti-FVIII antibodies in patients with hemophilia A who receive high doses of FVIII. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Factor VIII tolerance: is more better? Jay Lozier Blood 2005 106: 3334. [Full Text] [PDF] This article has been cited by other articles: 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] C. H. Miao, P. Ye, A. R. Thompson, D. J. Rawlings, and H. D. Ochs Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice Blood, July 1, 2006; 108(1): 19 - 27. [Abstract] [Full Text] [PDF]

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