PMID- 24126065
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20151119
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 20
IP  - 6
DP  - 2014 May
TI  - Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, 
      downregulated by interferon treatment, and affected by season.
PG  - 675-85
LID - 10.1177/1352458513507819 [doi]
AB  - 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.
FAU - Parnell, Grant P
AU  - Parnell GP
AD  - Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Gatt, Prudence N
AU  - Gatt PN
FAU - McKay, Fiona C
AU  - McKay FC
FAU - Schibeci, Stephen
AU  - Schibeci S
FAU - Krupa, Malgorzata
AU  - Krupa M
FAU - Powell, Joseph E
AU  - Powell JE
FAU - Visscher, Peter M
AU  - Visscher PM
FAU - Montgomery, Grant W
AU  - Montgomery GW
FAU - Lechner-Scott, Jeannette
AU  - Lechner-Scott J
FAU - Broadley, Simon
AU  - Broadley S
FAU - Liddle, Christopher
AU  - Liddle C
FAU - Slee, Mark
AU  - Slee M
FAU - Vucic, Steve
AU  - Vucic S
FAU - Stewart, Graeme J
AU  - Stewart GJ
FAU - Booth, David R
AU  - Booth DR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131014
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (Biomarkers)
RN  - 0 (Immunologic Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribosomal Protein S6)
RN  - 63231-63-0 (RNA)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Adult
MH  - Biomarkers/analysis
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Immunologic Factors/*therapeutic use
MH  - Interferon-beta/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/diagnosis/drug therapy/*metabolism
MH  - RNA/genetics
MH  - RNA, Messenger/*blood
MH  - Ribosomal Protein S6/*metabolism
MH  - *Seasons
MH  - Young Adult
OTO - NOTNLM
OT  - Multiple sclerosis
OT  - RPS6
OT  - biomarkers
OT  - interferon beta
OT  - season
EDAT- 2013/10/16 06:00
MHDA- 2015/03/31 06:00
CRDT- 2013/10/16 06:00
PHST- 2013/10/16 06:00 [entrez]
PHST- 2013/10/16 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - 1352458513507819 [pii]
AID - 10.1177/1352458513507819 [doi]
PST - ppublish
SO  - Mult Scler. 2014 May;20(6):675-85. doi: 10.1177/1352458513507819. Epub 2013 Oct 
      14.