title: Sex-specific prediction of interferon beta therapy response in relapsing-remitting multiple sclerosis.
abstract: Multiple sclerosis (MS) is a demyelinating disorder predominantly affecting young people. Currently, interferon beta (IFNβ) 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 IFNβ 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 IFNβ. We compared the expression profile of patients who responded to IFNβ treatment (n=16) and non-responsive IFNβ 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 IFNβ treatment response in male MS patients.
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Charbit
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Arriel
authors.initials: A
authors.lastname: Benis
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Geyshis
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Panayota
authors.initials: P
authors.lastname: Petrou
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Vaknin-Dembinsky
authors.affiliation: Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel. Electronic address: irisl@hadassah.org.il.
authors.forename: Iris
authors.initials: I
authors.lastname: Lavon
mesh_terms: D000328:Adult; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000235:genetics*; D012737:Sex Factors; D059467:Transcriptome
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta
keywords: Interferon beta; Multiple sclerosis; Sex; Therapy response