Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment
Entity
UAM. Departamento de MedicinaPublisher
ElsevierDate
2017-02-01Citation
10.1016/j.imbio.2016.09.002
Immunobiology 222.2 (2017): 363-371
ISSN
0171-2985DOI
10.1016/j.imbio.2016.09.002Funded by
In 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)Project
Gobierno de España. SAF2011-26583; Comunidad de Madrid. S2010/BMD-2316/COMPLEMENTOEditor's Version
http://dx.doi.org/10.1016/j.imbio.2016.09.002Subjects
Complement; Complement receptor 1; Eculizumab; extravascular hemolysis; PNH; MedicinaNote
Los datos asociados con este artículo están disponibles en: http://dx.doi.org/10.1016/j.imbio.2016.09.002.Rights
© 2016 Elsevier GmbHEsta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
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 administration
Files in this item
Google Scholar: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
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients
Marcos-Jiménez, Ana; Sánchez-Alonso, Santiago; Alcaraz-Serna, Ana; Esparcia, Laura; López-Sanz, Celia; Sampedro Núñez, Miguel Antonio; Mateu-Albero, Tamara; Sánchez-Cerrillo, Ildefonso; Martínez-Fleta, Pedro; Gabrie, Ligia; del Campo Guerola, Luciana; Rodríguez-Frade, José Miguel; Casasnovas, José M.; Reyburn, Hugh T.; Valés-Gómez, Mar; López Trascasa, Margarita; Martín-Gayo, Enrique; Calzada García, María Josefa; Castañeda Sanz, Santos; de la Fuente, Hortensia; González-Álvaro, Isidoro; Sánchez Madrid, Francisco; Muñoz Calleja, Cecilia; Alfranca González, Arantzazu
2021-03-01 -
Complement factor d (Adipsin) levels are elevated in acquired partial lipodystrophy (barraquer–simons syndrome)
Corvillo, Fernando; González-Sánchez, Laura; López-Lera, Alberto; Arjona, Emilia; Ceccarini, Giovanni; Santini, Ferruccio; Araújo-Vilar, David; Brown, Rebecca J.; Villarroya, Joan; Villarroya, Francesc; Rodríguez de Córdoba, Santiago; Caballero, Teresa; Nozal, Pilar; López Trascasa, Margarita
2021-06-21 -
Complement C5 protein as a marker of subclinical atherosclerosis
Martínez-López, Diego; Roldán-Montero, Raquel; García-Marqués, Fernando; Núñez, Estefanía; Jorge, Inmaculada; Camafeita, Emilio; Mínguez, Pablo; Rodriguez de Córdoba, Santiago; López-Melgar, Beatriz; Lara-Pezzi, Enrique; Fernández-Ortiz, Antonio; Ibáñez, Borja; Valdivielso, José Manuel; Fuster, Valentín; Michel, Jean-Baptiste; Blanco-Colio, Luis Miguel; Vázquez, Jesús; Martín Ventura, José Luis
2020-04-28