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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2011 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/43246 |
| Online Access: | https://hdl.handle.net/2445/43246 |
| Access Level: | Open access |
| Keyword: | Esclerosi múltiple Marcadors bioquímics Multiple sclerosis Biochemical markers |
| _version_ | 1878734912871202816 |
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| author | Malhotra, Sunny |
| 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 |
| author_browse | Bustamante, Marta F. Comabella, Manuel Deisenhammer, Florian Fissolo, Nicolás Malhotra, Sunny Montalbán Gairín, Xavier Nonell, Lara Nurtdinov, Ramil N. Perez Miralles, Francisco Ruiz de Villa, Carmen Río, Jordi Vegas Lozano, Esteban |
| 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_724aea2eddff78f2bb56cbd0da8ad30e |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/43246 |
| publishDate | 2011 |
| publishDateSort | 2011 |
| publisher | Public Library of Science (PLoS) |
| publisherStr | Public Library of Science (PLoS) |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis 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 Esclerosi múltiple Marcadors bioquímics Multiple sclerosis Biochemical markers 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. Public Library of Science (PLoS) https://hdl.handle.net/2445/43246 |
| spellingShingle | Search for Specific Biomarkers of IFNb Bioactivity in Patients with Multiple Sclerosis Malhotra, Sunny Esclerosi múltiple Marcadors bioquímics Multiple sclerosis Biochemical markers |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Esclerosi múltiple Marcadors bioquímics Multiple sclerosis Biochemical markers |
| topic_facet | Esclerosi múltiple Marcadors bioquímics Multiple sclerosis Biochemical markers |
| url | https://hdl.handle.net/2445/43246 |