SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-05-1475. This Article Full Text (PDF) All Versions of this Article: 2002-05-1475v1 102/3/887    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 Chang, M. Articles by Nugent, D. J Search for Related Content PubMed PubMed Citation Articles by Chang, M. Articles by Nugent, D. J Social Bookmarking                   What's this? Submitted May 20, 2002 Accepted March 27, 2003 Inhibition of megakaryocytopoiesis in vitro by immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies Mei Chang*, Peggy A Nakagawa, Shirley A Williams, Michael R Schwartz, Karen L Imfeld, Jeffrey S Buzby, and Diane J Nugent Children's Hospital of Orange County, Orange, CA, USA * Corresponding author; email: mchang{at}choc.org. To determine if megakaryocytes are targeted by ITP autoantibodies, as are platelets, we have studied the effects of ITP plasma on in vitro megakaryocytopoiesis. Umbilical cord blood mononuclear cells were incubated in the presence of thrombopoietin and 10% plasma from either ITP patients (n=53) or healthy donors. The yield of megakaryocytic cells, as determined by flow cytometry, was significantly reduced in the presence of ITP plasma containing anti-platelet glycoprotein (GP) Ib autoantibodies (p<0.001) as compared to both the control and patient plasma with no detectable anti-GP-IIb/IIIa or -Ib autoantibodies. Platelet absorbtion of anti-GP-Ib autoantibodies in ITP plasmas resulted in double the megakaryocyte production of the same plasmas without absorption, whereas platelet absorption of normal control plasma had no effect on megakaryocyte yield. Furthermore, two human monoclonal autoantibodies isolated from ITP patients, 2E7, specific for human platelet glycoprotein IIb heavy chain and 5E5, specific for a neoantigen on glycoprotein IIIa expressed on activated platelets, had significant inhibitory effects on in vitro megakaryocytopoiesis (p<0.001). Taken together, these data indicate that autoantibodies against either platelet GP-Ib or GP-IIb/IIIa in ITP plasma are not only involved in platelet destruction, but may also contribute to the inhibition of platelet production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. B. Bussel, G. Cheng, M. N. Saleh, B. Psaila, L. Kovaleva, B. Meddeb, J. Kloczko, H. Hassani, B. Mayer, N. L. Stone, et al. Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura N. Engl. J. Med., November 29, 2007; 357(22): 2237 - 2247. [Abstract] [Full Text] [PDF] D. M. Boruchov, S. Gururangan, M. C. Driscoll, and J. B. Bussel Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP) Blood, November 15, 2007; 110(10): 3526 - 3531. [Abstract] [Full Text] [PDF] J. B. Bussel, D. J. Kuter, J. N. George, R. McMillan, L. M. Aledort, G. T. Conklin, A. E. Lichtin, R. M. Lyons, J. Nieva, J. S. Wasser, et al. AMG 531, a Thrombopoiesis-Stimulating Protein, for Chronic ITP N. Engl. J. Med., October 19, 2006; 355(16): 1672 - 1681. [Abstract] [Full Text] [PDF] M. L. Webster, E. Sayeh, M. Crow, P. Chen, B. Nieswandt, J. Freedman, and H. Ni Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIb{alpha} antibodies Blood, August 1, 2006; 108(3): 943 - 946. [Abstract] [Full Text] [PDF] D. J. Nugent Immune Thrombocytopenic Purpura of Childhood Hematology, January 1, 2006; 2006(1): 97 - 103. [Abstract] [Full Text] [PDF] M. Sakakura, H. Wada, Y. Abe, J. Nishioka, H. Tomatsu, Y. Hamaguchi, S. Oguni, H. Shiku, and T. Nobori Usefulness of Measurement of Reticulated Platelets for Diagnosis of Idiopathic Thrombocytopenic Purpura Clinical and Applied Thrombosis/Hemostasis, July 1, 2005; 11(3): 253 - 261. [Abstract] [PDF] S. Kanaji, T. Kanaji, B. Jacquelin, M. Chang, D. J. Nugent, N. Komatsu, M. Moroi, K. Izuhara, and T. J. Kunicki Thrombopoietin initiates demethylation-based transcription of GP6 during megakaryocyte differentiation Blood, May 15, 2005; 105(10): 3888 - 3892. [Abstract] [Full Text] [PDF] R. McMillan and C. Durette Long-term outcomes in adults with chronic ITP after splenectomy failure Blood, August 15, 2004; 104(4): 956 - 960. [Abstract] [Full Text] [PDF] E. J. Houwerzijl, N. R. Blom, J. J. L. van der Want, M. T. Esselink, J. J. Koornstra, J. W. Smit, H. Louwes, E. Vellenga, and J. Th. M. de Wolf Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura Blood, January 15, 2004; 103(2): 500 - 506. [Abstract] [Full Text] [PDF] D. B. Cines, J. B. Bussel, R. B. McMillan, and J. L. Zehnder Congenital and Acquired Thrombocytopenia Hematology, January 1, 2004; 2004(1): 390 - 406. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020