title: Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season.
abstract: BACKGROUND
  Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system which responds to therapies targeting circulating immune cells.
  
  
  OBJECTIVE
  Our aim was to test if the T-cell activation gene expression pattern (TCAGE) we had previously described from whole blood was replicated in an independent cohort.
  
  
  METHODS
  We used RNA-seq to interrogate the whole blood transcriptomes of 72 individuals (40 healthy controls, 32 untreated MS). A cohort of 862 control individuals from the Brisbane Systems Genetics Study (BSGS) was used to assess heritability and seasonal expression. The effect of interferon beta (IFNB) therapy on expression was evaluated.
  
  
  RESULTS
  The MS/TCAGE association was replicated and rationalized to a single marker, ribosomal protein S6 (RPS6). Expression of RPS6 was higher in MS than controls (p<0.0004), and lower in winter than summer (p<4.6E-06). The seasonal pattern correlated with monthly UV light index (R=0.82, p<0.002), and was also identified in the BSGS cohort (p<0.0016). Variation in expression of RPS6 was not strongly heritable. RPS6 expression was reduced by IFNB therapy.
  
  
  CONCLUSIONS
  These data support investigation of RPS6 as a potential therapeutic target and candidate biomarker for measuring clinical response to IFNB and other MS therapies, and of MS disease heterogeneity.
authors.affiliation: Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Grant P
authors.initials: GP
authors.lastname: Parnell
authors.forename: Prudence N
authors.initials: PN
authors.lastname: Gatt
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McKay
authors.forename: Stephen
authors.initials: S
authors.lastname: Schibeci
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krupa
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Powell
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.forename: Simon
authors.initials: S
authors.lastname: Broadley
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Stewart
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood*; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D012621:Seasons; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D012313:RNA; D016899:Interferon-beta
keywords: Multiple sclerosis; RPS6; biomarkers; interferon beta; season