Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab
| Autor: | Lucio Luzzatto, Patrizia Ricci, Giorgio Fratellanza, Anna Paola Iori, Angela Amendola, Antonio M. Risitano, Giacomo Gianfaldoni, Francesco Rodeghiero, Andrea Camera, Rosario Notaro, Filippo Barbano, Eros Di Bona, Fiorella Alfinito, Ludovica Marando, Bruno Rotoli, Carla Boschetti, Elisa Seneca, Bianca Serio, Carmine Selleri, Alberto Zanella, Danilo Ranaldi |
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| Přispěvatelé: | Risitano, ANTONIO MARIA, Notaro, R, Marando, L, Serio, B, Ranaldi, D, Seneca, E, Ricci, P, Alfinito, Fiorella, Camera, A, Gianfaldoni, G, Amendola, A, Boschetti, C, Di Bona, E, Fratellanza, Giorgio, Barbano, F, Rodeghiero, F, Zanella, A, Iori, Ap, Selleri, Carmine, Luzzatto, L, Rotoli, B. |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Hemolytic anemia
Male medicine.medical_specialty Erythrocytes Cell Survival Immunology Hemoglobinuria Paroxysmal CD59 Antibodies Monoclonal Humanized Biochemistry Blood cell hemic and lymphatic diseases Internal medicine medicine Humans Hematology biology business.industry Antibodies Monoclonal hemic and immune systems Cell Biology Complement C3 Eculizumab medicine.disease Flow Cytometry Red blood cell medicine.anatomical_structure Paroxysmal nocturnal hemoglobinuria biology.protein Female Immunotherapy Antibody business circulatory and respiratory physiology medicine.drug |
| Popis: | 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 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 RBCs may constitute an additional disease mechanism in PNH, strongly enhanced by eculizumab treatment and producing a variable degree of extravascular hemolysis. |
| Databáze: | OpenAIRE |
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