title: Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis.
abstract: BACKGROUND
  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). 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.
  
  
  METHODS
  SPMS 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.
  
  
  RESULTS
  One 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.
  
  
  CONCLUSIONS
  Within 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.
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. Michael.Gurevich@sheba.health.gov.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Gurevich
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. gadi.miron@gmail.com.
authors.forename: Gadi
authors.initials: G
authors.lastname: Miron
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. rina.falb@sheba.health.gov.il.
authors.forename: Rina Zilkha
authors.initials: RZ
authors.lastname: Falb
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. Magalashvili@sheba.health.gov.il.
authors.forename: David
authors.initials: D
authors.lastname: Magalashvili
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. Mark.Dolev@sheba.health.gov.il.
authors.forename: Mark
authors.initials: M
authors.lastname: Dolev
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. Yael.Stern@sheba.health.gov.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Stern
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. Anat.Achiron@sheba.health.gov.il.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Anat.Achiron@sheba.health.gov.il.
authors.forename: Anat
authors.initials: A
authors.lastname: Achiron
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000235:genetics*; D012189:Retrospective Studies; D014158:Transcription, Genetic
chemical_list: D000276:Adjuvants, Immunologic; D000068556:Interferon beta-1a