Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment

Los datos asociados con este artículo están disponibles en: http://dx.doi.org/10.1016/j.imbio.2016.09.002.

Detalles Bibliográficos
Autores: Subías Hidalgo, Marta, Martin Merinero, Hector, López, Alicia, Anter, Jaouad, García, Sheila Pinto, Ataúlfo Gonzalez-Fernández, Fernando, Forés, Rafael, López Trascasa, Margarita, Villegas, Ana, Ojeda, Emilio, Rodríguez de Córdoba, Santiago
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/678272
Acceso en línea:http://hdl.handle.net/10486/678272
https://dx.doi.org/10.1016/j.imbio.2016.09.002
Access Level:acceso abierto
Palabra clave:Complement
Complement receptor 1
Eculizumab
extravascular hemolysis
PNH
Medicina
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spelling Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatmentSubías Hidalgo, MartaMartin Merinero, HectorLópez, AliciaAnter, JaouadGarcía, Sheila PintoAtaúlfo Gonzalez-Fernández, FernandoForés, RafaelLópez Trascasa, MargaritaVillegas, AnaOjeda, EmilioRodríguez de Córdoba, SantiagoComplementComplement receptor 1Eculizumabextravascular hemolysisPNHMedicinaLos datos asociados con este artículo están disponibles en: http://dx.doi.org/10.1016/j.imbio.2016.09.002.Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by complement-mediated intravascular hemolysis that is effectively treated with eculizumab. However, treatment responses are reported heterogeneous with some patients presenting residual hemolysis and requiring RBC transfusions. Recent reports have shown that both extravascular hemolysis and incomplete C5 blockade can explain these suboptimal hematological responses. Here we have tested our eculizumab-treated PNH patients (n = 12) for signs of hemolysis and assessed complement biomarkers. Patients were also genotyped for complement receptor 1 (CR1, CD35) and C5 polymorphisms and evaluated for free eculizumab in plasma. We report that 10 patients (83%) present parameters suggesting persistent hemolysis, although they did not require additional transfusions. Seven of them (58%) become direct Coombs-test positive as a consequence of treatment, including all patients carrying the low-expression CR1-L allele. CH50 and sC5b-9 assays demonstrate that the persistent low-level hemolysis identified in our treated patients is not a consequence of incomplete C5 blockade, supporting that this hemolysis, as has been suggested previously, results from the extravascular removal of C3 opsonized PNH erythrocytes. We also show that continuous alternative pathway activation in eculizumab-treated individuals carrying the CR1-L allele results in abnormally decreased levels of C3 in plasma that could, potentially, increase their susceptibility to bacterial infections. Finally, we encourage a routine evaluation of free eculizumab levels and terminal pathway activity to personalize eculizumab administrationIn this study S.R de C. is supported by the Spanish “Ministerio de Economía y Competitividad” (SAF2011-26583) and the Autonomous Region of Madrid (S2010/BMD-2316)ElsevierDepartamento de MedicinaFacultad de Medicina20172017-02-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/678272https://dx.doi.org/10.1016/j.imbio.2016.09.002reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6782722026-06-23T12:46:27Z
dc.title.none.fl_str_mv Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
title Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
spellingShingle Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
Subías Hidalgo, Marta
Complement
Complement receptor 1
Eculizumab
extravascular hemolysis
PNH
Medicina
title_short Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
title_full Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
title_fullStr Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
title_full_unstemmed Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
title_sort Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
dc.creator.none.fl_str_mv Subías Hidalgo, Marta
Martin Merinero, Hector
López, Alicia
Anter, Jaouad
García, Sheila Pinto
Ataúlfo Gonzalez-Fernández, Fernando
Forés, Rafael
López Trascasa, Margarita
Villegas, Ana
Ojeda, Emilio
Rodríguez de Córdoba, Santiago
author Subías Hidalgo, Marta
author_facet Subías Hidalgo, Marta
Martin Merinero, Hector
López, Alicia
Anter, Jaouad
García, Sheila Pinto
Ataúlfo Gonzalez-Fernández, Fernando
Forés, Rafael
López Trascasa, Margarita
Villegas, Ana
Ojeda, Emilio
Rodríguez de Córdoba, Santiago
author_role author
author2 Martin Merinero, Hector
López, Alicia
Anter, Jaouad
García, Sheila Pinto
Ataúlfo Gonzalez-Fernández, Fernando
Forés, Rafael
López Trascasa, Margarita
Villegas, Ana
Ojeda, Emilio
Rodríguez de Córdoba, Santiago
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv Complement
Complement receptor 1
Eculizumab
extravascular hemolysis
PNH
Medicina
topic Complement
Complement receptor 1
Eculizumab
extravascular hemolysis
PNH
Medicina
description Los datos asociados con este artículo están disponibles en: http://dx.doi.org/10.1016/j.imbio.2016.09.002.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-02-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/678272
https://dx.doi.org/10.1016/j.imbio.2016.09.002
url http://hdl.handle.net/10486/678272
https://dx.doi.org/10.1016/j.imbio.2016.09.002
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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