English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/149512
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

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

Other TitlesHemolysis in eculizumab-treated PNH patients
AuthorsSubías, Marta; Martín Merinero, Héctor; López, Alicia; Anter, Jauoad; Pinto, Sheila ; Rodríguez de Córdoba, Santiago
KeywordsPNH
Complement
Extravascular hemolysis
Complement receptor 1
Eculizumab
Issue DateFeb-2017
PublisherElsevier
CitationImmunobiology 222 (2)363–371 (2017)
AbstractParoxysmal 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 administration.
Description35 p.-3 fig.-4 tab. Subías, Marta et al.
Publisher version (URL)https://doi.org/10.1016/j.imbio.2016.09.002
URIhttp://hdl.handle.net/10261/149512
DOI10.1016/j.imbio.2016.09.002
ISSN0171-2985
E-ISSN1878-3279
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
2017-Immunobiology-Postprint_COMPLETO.pdfPostprint992,55 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.