SEARCH:   Advanced

Blood, 1 April 2006, Vol. 107, No. 7, pp. 2976-2983. Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-06-2562. This Article Full Text (PDF) All Versions of this Article: 2005-06-2562v1 107/7/2976    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 Ni, H. Articles by Freedman, J. Search for Related Content PubMed PubMed Citation Articles by Ni, H. Articles by Freedman, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 29, 2005 Accepted November 16, 2005 A novel murine model of fetal and neonatal alloimmune thrombocytopenia:Response to intravenous IgG therapy Heyu Ni*, Pingguo Chen, Christopher M Spring, Ebrahim Sayeh, John W Semple, Alan H Lazarus, Richard O Hynes, and John Freedman Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Canadian Blood Services, Canada; The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, Ontario, Canada Canadian Blood Services, Canada; The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, Ontario, Canada The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada * Corresponding author; email: nih{at}smh.toronto.on.ca. Fetal and neonatal alloimmune thrombocytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (3 integrin). Here we have established a novel animal model of FNAITP using 3 integrin-deficient (3-/-) mice. We demonstrated first that these mice are immunoresponsive to 3 integrin; 3-/- mice transfused with wild-type platelets generated specific anti-3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently 3-/- female mice (both naive and immunized) were bred with wild-type male mice to recapitulate the features of FNAITP. The titer of generated maternal antibodies correlated with the severity of FNAITP. High titer maternal anti-3 antibodies caused severe fetal thrombocytopenia, intracranial hemorrhage, and even miscarriage. Furthermore, maternal administration of intravenous IgG ameliorated FNAITP and downregulated pathogenic antibodies in both the maternal and fetal circulations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Nishie, D. Sawamura, K. Natsuga, S. Shinkuma, M. Goto, A. Shibaki, H. Ujiie, E. Olasz, K. B. Yancey, and H. Shimizu A Novel Humanized Neonatal Autoimmune Blistering Skin Disease Model Induced by Maternally Transferred Antibodies J. Immunol., September 15, 2009; 183(6): 4088 - 4093. [Abstract] [Full Text] [PDF] A. Reheman, H. Yang, G. Zhu, W. Jin, F. He, C. M. Spring, X. Bai, P. L. Gross, J. Freedman, and H. Ni Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor Blood, February 19, 2009; 113(8): 1809 - 1817. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020