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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2619-2626. Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-03-0989. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-0989v1 107/7/2619    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Armour, K. L. Articles by Williamson, L. M. Search for Related Content PubMed PubMed Citation Articles by Armour, K. L. Articles by Williamson, L. M. Related Collections Red Cells Immunotherapy Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity Kathryn L. Armour, David R. Parry-Jones, Nigel Beharry, James R. Ballinger, Rosey Mushens, R. Keith Williams, Cynthia Beatty, Simon Stanworth, Paul Lloyd-Evans, Marion Scott, Michael R. Clark, A. Michael Peters, and Lorna M. Williamson From the Departments of Pathology, Radiology, and Haematology, University of Cambridge; the Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge; National Blood Service, Bristol and Cambridge; and the National Blood Service Clinical Biotechnology Centre, Bristol, United Kingdom. Alloimmune feto-maternal destruction of blood cells is thought to be mediated by binding of alloantibodies to Fc receptors on effector cells. Blocking the antigen using inert antibodies might prolong cell survival. We have performed a "proof of principle" study in volunteers to measure the intravascular survival of autologous red cells coated with human recombinant IgG antibody containing a novel constant region, G1nab, devoid of in vitro cytotoxic activity. RhD-positive red blood cells (RBCs), labeled with chromium-51 or technetium-99m, were separately coated to equal levels with wild-type IgG1 or G1nab anti-D antibody (Fog-1). After re-injection, there was complete, irreversible clearance of IgG1-coated RBCs by 200 minutes, concomitant with appearance of radiolabel in plasma. Gamma camera imaging revealed accumulation in spleen and, at higher coating levels, in liver. In contrast, clearance of G1nab-coated cells was slower, incomplete, and transient, with whole blood counts falling to 7% to 38% injected dose by about 200 minutes before increasing to 12% to 67% thereafter. There was no appearance of plasma radiolabel and no hepatic accumulation. These findings suggest that G1nab-coated RBCs were not hemolysed but temporarily sequestered in the spleen and that our approach merits investigation in larger studies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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