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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2131-2137. Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-02-0782. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0782v1 107/5/2131    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 Hill, A. Articles by Hillmen, P. Search for Related Content PubMed PubMed Citation Articles by Hill, A. Articles by Hillmen, P. Related Collections Immunobiology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Protection of erythrocytes from human complement–mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy Anita Hill, Simon H. Ridley, Dirk Esser, Rodney G. Oldroyd, Matthew J. Cullen, Paula Kareclas, Seán Gallagher, Geoffrey P. Smith, Stephen J. Richards, Jennifer White, Richard A. G. Smith, and Peter Hillmen From the Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals National Health Service (NHS) Trust, Leeds; Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; and Adprotech, Inflazyme Pharmaceuticals, Richmond, BC, Canada. Paroxysmal nocturnal hemoglobinuria (PNH) results from the expansion of a hematopoietic clone that is deficient in glycosylphosphatidylinositol-anchored molecules. PNH is characterized by chronic hemolysis with acute exacerbations due to the uncontrolled activity of complement on PNH cells, which lack the inhibitor of homologous complement, CD59. Symptoms include severe fatigue, hemoglobinuria, esophageal spasm, erectile dysfunction, and thrombosis. We report the use of a novel synthetically modified recombinant human CD59, rhCD59-P, a soluble protein that attaches to cell membranes. In vitro treatment of PNH erythrocytes with rhCD59-P resulted in levels of CD59 equivalent to normal erythrocytes and effectively protected erythrocytes from complement-mediated hemolysis. The administration of rhCD59-P to CD1 mice resulted in levels of CD59 on erythrocytes, which protected them from complement-mediated lysis. Thus, rhCD59-P corrects the CD59 deficiency in vitro and can bind to erythrocytes in an in vivo murine model, protecting the cells from the activity of human complement, and represents a potential therapeutic strategy in PNH. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Davis Eculizumab Am. J. Health Syst. Pharm., September 1, 2008; 65(17): 1609 - 1615. [Abstract] [Full Text] [PDF] C. E. Bowles, I. Wilkinson, R. A. G. Smith, A. J. G. Moir, H. Montgomery, and R. J. M. Ross Membrane Reinsertion of a Myristoyl-Peptidyl Anchored Extracellular Domain Growth Hormone Receptor Endocrinology, February 1, 2007; 148(2): 824 - 830. [Abstract] [Full Text] [PDF]

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