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Blood, 1 August 2005, Vol. 106, No. 3, pp. 929-931. Prepublished online as a Blood First Edition Paper on April 21, 2005; DOI 10.1182/blood-2004-12-4955. This Article Full Text (PDF) All Versions of this Article: 2004-12-4955v1 106/3/929    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 Suvarna, S. Articles by Arepally, G. Search for Related Content PubMed PubMed Citation Articles by Suvarna, S. Articles by Arepally, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 3, 2005 Accepted March 25, 2005 PF4/Heparin complexes are T-cell dependent antigens Shayela Suvarna, Lubica Rauova, Emily K McCracken, Christina M Goss, Bruce S Sachais, Steven E McKenzie, Michael P Reilly, Michael D Gunn, Douglas B Cines, Mortimer Poncz, and Gowthami Arepally* Division of Hematology, Duke University Medical Center, Durham, NC, USA Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Cardeza Foundation for Hematologic Research, Philadelphia, PA, USA Devision of Cardiology, Duke University Medical Center, Durham, NC, USA Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA * Corresponding author; email: arepa001{at}mc.duke.edu. Heparin-Induced Thrombocytopenia (HIT) is a life-threatening, thrombotic disorder associated with development of anti-PF4/heparin autoantibodies. Little is known about the antigenic and cellular requirements that initiate the immune response to these complexes. To begin to delineate mechanisms of autoantibody formation in HIT, we studied the immunizing effects of murine PF4 (mPF4)/heparin in mice with and without thymic function. Euthymic mice were injected with mPF4/heparin complexes, mPF4, heparin or buffer. Mice injected with mPF4/heparin, but not mPF4 or heparin alone, developed heparin-dependent autoantibodies that shared serologic and functional characteristics of human HIT antibodies, including preferential binding to mPF4/heparin complexes and causing heparin- and FcRgIIA-dependent platelet activation. In contrast, athymic mice did not develop HIT-like antibodies. Taken together, these studies establish that PF4/heparin complexes are highly immunogenic and elicit self-reacting anti-PF4/heparin antibodies in a T-cell dependent manner. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Greinacher, T. Kohlmann, U. Strobel, J.-A. I. Sheppard, and T. E. Warkentin The temporal profile of the anti-PF4/heparin immune response Blood, May 14, 2009; 113(20): 4970 - 4976. [Abstract] [Full Text] [PDF] S. Suvarna, B. Espinasse, R. Qi, R. Lubica, M. Poncz, D. B. Cines, M. R. Wiesner, and G. M. Arepally Determinants of PF4/heparin immunogenicity Blood, December 15, 2007; 110(13): 4253 - 4260. [Abstract] [Full Text] [PDF]

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