Document Detail

Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab.
MedLine Citation:
PMID:  19179465     Owner:  NLM     Status:  MEDLINE    
In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is due mainly to deficiency of the complement regulator CD59 on the surface of red blood cells (RBCs). Eculizumab, an antibody that targets complement fraction 5 (C5), has proven highly effective in abolishing complement-mediated intravascular hemolysis in PNH; however, the hematologic 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(-)). The proportion of C3(+) RBCs correlated significantly with the reticulocyte count and with the hematologic response to eculizumab. In 3 patients in whom (51)Cr labeling of RBCs was carried out while on eculizumab, we have demonstrated reduced RBC half-life in vivo, with excess (51)Cr uptake in spleen and in liver. Binding of C3 by PNH RBCs may constitute an additional disease mechanism in PNH, strongly enhanced by eculizumab treatment and producing a variable degree of extravascular hemolysis.
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; Bruno Rotoli
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Publication Detail:
Type:  Journal Article     Date:  2009-01-29
Journal Detail:
Title:  Blood     Volume:  113     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-05-08     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4094-100     Citation Subset:  AIM; IM    
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MeSH Terms
Antibodies, Monoclonal / immunology*,  therapeutic use*
Antibodies, Monoclonal, Humanized
Cell Survival
Complement C3 / metabolism*
Erythrocytes / metabolism*,  pathology
Flow Cytometry
Hemoglobinuria, Paroxysmal / immunology,  metabolism*,  therapy*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Complement C3; A3ULP0F556/eculizumab

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