Abstract
BackgroundInterferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available. Our aim was to identify a subgroup of SPMS patients presenting a gene expression signature similar to that of RRMS patients who are clinical responders to IFN treatment.MethodsSPMS patients (n = 50, 20 IFN treated and 30 untreated) were classified using unsupervised hierarchical clustering according to IFN inducible gene expression profile identified in RRMS clinical responders to treatment. IFN inducible gene expression profile was determined by finding differentially expressed genes (DEGs) between IFN treated (n = 10) and untreated (n = 25) RRMS patients. Validation was performed on an additional independent group of 27 SPMS IFN treated patients by qRT-PCR.ResultsOne hundred and four DEGs, enriched by IFN signaling pathway (p = 7.4E-08), were identified in IFN treated RRMS patients. Classification of SPMS patients based on these DEGs yielded two patient groups: (1) IFN transcriptional responders (n = 12, 60 % of SPMS treated patients) showing gene-expression profile similar to IFN treated RRMS patients; (2) IFN transcriptional non-responders (n = 8) showing expression profile similar to untreated patients. IFN transcriptional responders were characterized by a more active disease, as defined by higher EDSS progression and annual relapse rate.ConclusionWithin the IFN treated SPMS population, 60 % of patients have a transcriptional response to IFN which is similar to that of RRMS patients who are IFN responders to treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0495-x) contains supplementary material, which is available to authorized users.
Highlights
Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS)
IFN inducible transcriptional profile associated with good clinical response to treatment in RRMS patients IFN treated RRMS patients with good clinical response to treatment (n = 10, mean age 40.9 ± 2.3 years, 4 females, disease duration 5.9 ± 1.5 years, Extended disability status score (EDSS) 1.6 ± 0.4), were compared to untreated RRMS patients (n = 25, age 38.1 ± 1.0 years, 16 females, disease duration 7.2 ± 1.1 years, EDSS 2.4 ± 0.2)
We further expanded this concept by demonstrating that within our cohort of SPMS patients, 60 % characterized by active disease had blood transcriptional signature of response to IFN treatment similar to that of RRMS patients that were good clinical responders to treatment
Summary
Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). The European trial has shown IFN beta-1b delayed progression of disability whereas in the American trial this finding was not replicated. These contradictory results have subsequently been attributed to differing clinical characteristics of patients enrolled in trials, with better treatment outcome associated with patients at an earlier, more active stage of disease as demonstrated by shorter disease duration and higher relapse rate prior to trial initiation [9]. As there is a heterogeneous clinical response to treatment in SPMS, it is important to discover biomarkers which can help identify those patients who could benefit most from therapy
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