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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 24, 2005 Accepted August 23, 2005 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, Sean Gallagher, Geoffrey P Smith, Stephen J Richards, Jennifer White, Richard Smith, and Peter Hillmen HMDS, Leeds Teaching Hospitals NHS Trust, Leeds, W Yorks, United Kingdom Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Cambridge, Cambridgeshire, United Kingdom; Adprotech Ltd, Inflazyme Pharmaceuticals,, Richmond, British Columbia, Canada Adprotech Ltd, Inflazyme Pharmaceuticals,, Richmond, British Columbia, Canada * Corresponding author; email: anitahill{at}nhs.net. Paroxysmal nocturnal hemoglobinuria (PNH) results from a hematopoeitic clone which 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 resulting from the deficiency of 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-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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