Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis

Myxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS). However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenes...

Descripción completa

Detalles Bibliográficos
Autores: Malhotra, Sunny, Bustamante, Marta F., Perez Miralles, Francisco, Río, Jordi, Ruiz de Villa, Carmen, Vegas Lozano, Esteban, Nonell, Lara, Deisenhammer, Florian, Fissolo, Nicolás, Nurtdinov, Ramil N., Montalbán Gairín, Xavier, Comabella, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/43246
Acceso en línea:https://hdl.handle.net/2445/43246
Access Level:acceso abierto
Palabra clave:Esclerosi múltiple
Marcadors bioquímics
Multiple sclerosis
Biochemical markers
id ES_724aea2eddff78f2bb56cbd0da8ad30e
oai_identifier_str oai:recercat.cat:2445/43246
network_acronym_str ES
network_name_str España
repository_id_str
spelling Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple SclerosisMalhotra, SunnyBustamante, Marta F.Perez Miralles, FranciscoRío, JordiRuiz de Villa, CarmenVegas Lozano, EstebanNonell, LaraDeisenhammer, FlorianFissolo, NicolásNurtdinov, Ramil N.Montalbán Gairín, XavierComabella, ManuelEsclerosi múltipleMarcadors bioquímicsMultiple sclerosisBiochemical markersMyxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS). However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis.Public Library of Science (PLoS)2013201320112013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/43246Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0023634PLoS One, 2011, vol. 6, num. 8, p. e23634http://dx.doi.org/10.1371/journal.pone.0023634info:eu-repo/grantAgreement/EC/FP7/212877cc-by (c) Malhotra, S. et al., 2011http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/432462026-05-29T05:05:01Z
dc.title.none.fl_str_mv Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
title Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
spellingShingle Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
Malhotra, Sunny
Esclerosi múltiple
Marcadors bioquímics
Multiple sclerosis
Biochemical markers
title_short Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
title_full Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
title_fullStr Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
title_full_unstemmed Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
title_sort Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis
dc.creator.none.fl_str_mv Malhotra, Sunny
Bustamante, Marta F.
Perez Miralles, Francisco
Río, Jordi
Ruiz de Villa, Carmen
Vegas Lozano, Esteban
Nonell, Lara
Deisenhammer, Florian
Fissolo, Nicolás
Nurtdinov, Ramil N.
Montalbán Gairín, Xavier
Comabella, Manuel
author Malhotra, Sunny
author_facet Malhotra, Sunny
Bustamante, Marta F.
Perez Miralles, Francisco
Río, Jordi
Ruiz de Villa, Carmen
Vegas Lozano, Esteban
Nonell, Lara
Deisenhammer, Florian
Fissolo, Nicolás
Nurtdinov, Ramil N.
Montalbán Gairín, Xavier
Comabella, Manuel
author_role author
author2 Bustamante, Marta F.
Perez Miralles, Francisco
Río, Jordi
Ruiz de Villa, Carmen
Vegas Lozano, Esteban
Nonell, Lara
Deisenhammer, Florian
Fissolo, Nicolás
Nurtdinov, Ramil N.
Montalbán Gairín, Xavier
Comabella, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Esclerosi múltiple
Marcadors bioquímics
Multiple sclerosis
Biochemical markers
topic Esclerosi múltiple
Marcadors bioquímics
Multiple sclerosis
Biochemical markers
description Myxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS). However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis.
publishDate 2011
dc.date.none.fl_str_mv 2011
2013
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/43246
url https://hdl.handle.net/2445/43246
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0023634
PLoS One, 2011, vol. 6, num. 8, p. e23634
http://dx.doi.org/10.1371/journal.pone.0023634
info:eu-repo/grantAgreement/EC/FP7/212877
dc.rights.none.fl_str_mv cc-by (c) Malhotra, S. et al., 2011
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Malhotra, S. et al., 2011
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410713833832448
score 15,81155

Similares en LA Referencia