Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

Parnell, Grant P., Gatt, Prudence N., McKay, Fiona C., Schibeci, Stephen, Krupa, Malgorzata, Powell, Joseph E., Visscher, Peter M., Montgomery, Grant W., Lechner-Scott, Jeannette, Broadley, Simon, Liddle, Christopher, Slee, Mark, Vucic, Steve, Stewart, Graeme J. and Booth, David R. (2013) Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season. Multiple Sclerosis, 20 6: 675-685. doi:10.1177/1352458513507819

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Author Parnell, Grant P.
Gatt, Prudence N.
McKay, Fiona C.
Schibeci, Stephen
Krupa, Malgorzata
Powell, Joseph E.
Visscher, Peter M.
Montgomery, Grant W.
Lechner-Scott, Jeannette
Broadley, Simon
Liddle, Christopher
Slee, Mark
Vucic, Steve
Stewart, Graeme J.
Booth, David R.
Title Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season
Journal name Multiple Sclerosis   Check publisher's open access policy
ISSN 1352-4585
1477-0970
Publication date 2013-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1177/1352458513507819
Open Access Status File (Author Post-print)
Volume 20
Issue 6
Start page 675
End page 685
Total pages 11
Place of publication London, United Kingdom
Publisher Sage Publications
Language eng
Formatted 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.
Keyword Multiple sclerosis
Biomarkers
RPS6
Season
Interferon beta
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
UQ Diamantina Institute Publications
 
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Created: Wed, 12 Mar 2014, 00:45:35 EST by Debra McMurtrie on behalf of Queensland Brain Institute