Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria
| Autor: | Maria De Angioletti, Patrizia Ricci, Michela Sica, Wilma Barcellini, Antonio M. Risitano, Tommaso Rondelli, Anna Paola Iori, Lucio Luzzatto, Carla Boschetti, Véronique Frémeaux-Bacchi, Benedetta Peruzzi, Rosario Notaro, Régis Peffault de Latour, Veronica Valle, Gérard Socié |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Blood transfusion Genotype Complement receptor 1 medicine.medical_treatment Hemoglobinuria Paroxysmal HindIII Antibodies Monoclonal Humanized complement blockade intravascular hemolysis Internal medicine medicine Humans Blood Transfusion pharmacogenetics Polymorphism Genetic biology Complement C4 Complement C3 Articles Hematology Eculizumab Paroxysmal Nocturnal Hemoglobinuria medicine.disease extravascular hemolysis Red blood cell Endocrinology medicine.anatomical_structure Immunology Receptors Complement 3b biology.protein Paroxysmal nocturnal hemoglobinuria Female biology.gene Pharmacogenetics Follow-Up Studies medicine.drug |
| Zdroj: | Haematologica (Roma) 99 (2014): 262–266. doi:10.3324/haematol.2013.090001 info:cnr-pdr/source/autori:Rondelli, Tommaso; Risitano, Antonio Maria; Peffault de Latour, Regis; Sica, Michela; Peruzzi, Benedetta; Ricci, Patrizia, Barcellini, Wanda; Iori, Anna Paola; Boschetti, Carla; Valle, Veronica; Frémeaux-Bacchi, Veronique; De Angioletti, Maria; Socié, Gerard; Luzzatto, Lucio; Notaro, Rosario./titolo:Polymorphism of the complement receptor 1 gene correlates with hematological response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria./doi:10.3324%2Fhaematol.2013.090001/rivista:Haematologica (Roma)/anno:2014/pagina_da:262/pagina_a:266/intervallo_pagine:262–266/volume:99 |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2013.090001 |
| Popis: | Complement blockade by eculizumab is clinically effective in hemolytic paroxysmal nocturnal hemoglobinuria. However, the response is variable and some patients remain dependent on red blood cell transfusions. In 72 patients with hemolytic paroxysmal nocturnal hemoglobinuria on eculizumab we tested the hypothesis that response may depend on genetic polymorphisms of complement-related genes. We found no correlation between the complement component C3 genotypes and the need for blood transfusions. On the other hand, we found a significant correlation with the HindIII polymorphism of a complement regulatory gene, the complement receptor 1 (CR1) gene. At this locus two co-dominant alleles are known, of which H (common) is associated with high expression, whereas L (rare) is associated with low expression of CR1 on red blood cells. Patients who still needed blood transfusion on eculizumab accounted for 18% of the H/H homozygotes, 33% of the H/L heterozygotes and 68% of the L/L homozygotes (P=0.016). Thus, patients with paroxysmal nocturnal hemoglobinuria who have the L/L genotype are seven times more likely to be sub-optimal responders to eculizumab. Both in vitro and in vivo we found that the CR1 HindIII genotype correlates with the abundance of paroxysmal nocturnal hemoglobinuria red cells that have bound C3, and with the kinetics of C3 binding. These results are consistent with the notion that by affecting C3 binding the CR1 genotype influences the response to eculizumab treatment, and this emerges as a novel example of pharmacogenetics. |
| Databáze: | OpenAIRE |
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