Sex-specific prediction of interferon beta therapy response in relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disorder predominantly affecting young people. Currently, interferon beta (IFN beta) is a common treatment for MS. Despite a large effort in recent years, valid biomarkers with predictive value for clinical outcome and response to therapy are lacking. In order to identify predictive biomarkers of response to IFN beta therapy in relapsing-remitting MS patients, we analyzed expression of 526 immune-related genes with the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA) on total RNA extracted from peripheral blood mononuclear cells of 30 relapsing-remitting MS patients. We used a Wilcoxon signed-rank test to find an association between certain gene expression profiles and clinical responses to IFN beta. We compared the expression profile of patients who responded to IFNI?. treatment (n = 16) and non-responsive IFN beta patients (n = 14). The analysis revealed that the expression of eight genes could differentiate between responsive and non-responsive men (p <= 0.005). This differentiation was not evident in women. We analyzed results from an additional cohort of 47 treated and untreated patients to validate the results and explore whether this eight gene cluster could also predict treatment response. Analysis of the validation cohort demonstrated that three out of the eight genes remained significant in only the treated men (p <= 0.05). Our findings could be used as a basis for establishing a routine test for objective prediction of IFN beta treatment response in male MS patients. (C) 2015 Elsevier Ltd. All rights reserved.