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 LuzzattoBruno Rotoli

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4094-4100
Number of pages7
JournalBlood
Volume113
Issue number17
DOIs
Publication statusPublished - 2009

Fingerprint

Paroxysmal Hemoglobinuria
Complement C3
Blood
Erythrocytes
Hemolysis
Complement C5
Reticulocyte Count
eculizumab
Flow cytometry
Hemolytic Anemia
Liver
Labeling
Half-Life
Flow Cytometry
Spleen
Cells
Phenotype

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. / Risitano, Antonio M.; Notaro, Rosario; Marando, Ludovica; Serio, Bianca; Ranaldi, Danilo; Seneca, Elisa; Ricci, Patrizia; Alfinito, Fiorella; Camera, Andrea; Gianfaldoni, Giacomo; Amendola, Angela; Boschetti, Carla; Di Bona, Eros; Fratellanza, Giorgio; Barbano, Filippo; Rodeghiero, Francesco; Zanella, Alberto; Iori, Anna Paola; Selleri, Carmine; Luzzatto, Lucio; Rotoli, Bruno.

In: Blood, Vol. 113, No. 17, 2009, p. 4094-4100.

Research output: Contribution to journalArticle

Risitano, AM, Notaro, R, Marando, L, Serio, B, Ranaldi, D, Seneca, E, Ricci, P, Alfinito, F, Camera, A, Gianfaldoni, G, Amendola, A, Boschetti, C, Di Bona, E, Fratellanza, G, Barbano, F, Rodeghiero, F, Zanella, A, Iori, AP, Selleri, C, Luzzatto, L & Rotoli, B 2009, 'Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab', Blood, vol. 113, no. 17, pp. 4094-4100. https://doi.org/10.1182/blood-2008-11-189944
Risitano, Antonio M. ; Notaro, Rosario ; Marando, Ludovica ; Serio, Bianca ; Ranaldi, Danilo ; Seneca, Elisa ; Ricci, Patrizia ; Alfinito, Fiorella ; Camera, Andrea ; Gianfaldoni, Giacomo ; Amendola, Angela ; Boschetti, Carla ; Di Bona, Eros ; Fratellanza, Giorgio ; Barbano, Filippo ; Rodeghiero, Francesco ; Zanella, Alberto ; Iori, Anna Paola ; Selleri, Carmine ; Luzzatto, Lucio ; Rotoli, Bruno. / Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. In: Blood. 2009 ; Vol. 113, No. 17. pp. 4094-4100.
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AU - Serio, Bianca

AU - Ranaldi, Danilo

AU - Seneca, Elisa

AU - Ricci, Patrizia

AU - Alfinito, Fiorella

AU - Camera, Andrea

AU - Gianfaldoni, Giacomo

AU - Amendola, Angela

AU - Boschetti, Carla

AU - Di Bona, Eros

AU - Fratellanza, Giorgio

AU - Barbano, Filippo

AU - Rodeghiero, Francesco

AU - Zanella, Alberto

AU - Iori, Anna Paola

AU - Selleri, Carmine

AU - Luzzatto, Lucio

AU - Rotoli, Bruno

PY - 2009

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