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...

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Bibliographic Details
Authors: 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
Format: article
Status:Published version
Publication Date:2011
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/43246
Online Access:https://hdl.handle.net/2445/43246
Access Level:Open access
Keyword:Esclerosi múltiple
Marcadors bioquímics
Multiple sclerosis
Biochemical markers
Description
Summary: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.

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