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Blood, 23 April 2009, Vol. 113, No. 17, pp. 4094-4100. Prepublished online as a Blood First Edition Paper on January 29, 2009; DOI 10.1182/blood-2008-11-189944. This Article Full Text (PDF) All Versions of this Article: blood-2008-11-189944v1 113/17/4094    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 Risitano, A. M. Articles by Rotoli, B. Search for Related Content PubMed PubMed Citation Articles by Risitano, A. M. Articles by Rotoli, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 24, 2008 Accepted January 17, 2009 Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab Antonio M. Risitano*, Rosario Notaro, Ludovica Marando, Bianca Serio, Danilo Ranaldi, Elisa Seneca, Patrizia Ricci, Fiorella Alfinito, Andrea Camera, Giacomo Gianfaldoni, Angela Amendola, Carla Boschetti, Eros Di Bona, Giorgio Fratellanza, Filippo Barbano, Francesco Rodeghiero, Alberto Zanella, Anna Paola Iori, Carmine Selleri, Lucio Luzzatto, and Bruno Rotoli Hematology, Department of Biochemistry and Medical Biotechnologies, Federico II University, Naples, Italy Laboratory of Genetics and Gene Transfer, Core Research Laboratory - Istituto, Toscano Tumori (CRL-ITT), Florence, Italy Department of Hematology, University of Florence, Florence, Italy Department of Cellular Biotechnologies and Hematology, La Sapienza University, Rome, Italy Department of Hematology, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy Department of Cell Therapy and Hematology, Hemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy Immunohematology and Transfusion Medicine, Federico II University, Naples, Italy Department of Nuclear Medicine, IRCCS Hospital Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), Italy Core Research Laboratory - Istituto, Toscano Tumori (CRL-ITT), Florence, Italy * Corresponding author; email: amrisita{at}unina.it. In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is mainly due to deficiency of the complement regulator CD59 on the surface of RBCs. Eculizumab, an antibody that targets complement fraction 5 (C5), has proven highly effective in abolishing complement-mediated intravascular hemolysis in PNH: however, the hematological benefit varies considerably among patients. In the aim to understand the basis for this variable response, we have investigated by flow cytometry the binding of complement fraction 3 (C3) on RBCs from PNH patients before and during eculizumab treatment. There was no evidence of C3 on RBCs of untreated PNH patients; by contrast, in all patients on eculizumab (n = 41) a substantial fraction of RBCs had C3 bound on their surface, and this was entirely restricted to RBCs with the PNH phenotype (CD59-neg). The proportion of C3+ RBCs correlated significantly with the reticulocyte count and with the hematological response to eculizumab. In 3 patients in whom 51Cr labeling of RBCs was carried out while on eculizumab, we have demonstrated reduced RBC half-life in vivo, with excess 51Cr uptake in spleen and in liver. Binding of C3 by PNH RBC may constitute an additional disease mechanism in PNH, strongly enhanced by eculizumab treatment and producing a variable degree of extravascular hemolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. A. Brodsky How I treat paroxysmal nocturnal hemoglobinuria Blood, June 25, 2009; 113(26): 6522 - 6527. [Abstract] [Full Text] [PDF]

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