Openly accessible

Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease

Ellis, Justine A, Munro, Jane E, Chavez, Raul A, Gordon, Lavinia, Joo, Jihoon E, Akikusa, Jonathan D, Allen, Roger C, Ponsonby, Anee-Louise, Craig, Jeffrey M and Saffery, Richard 2012, Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease, Clinical epigenetics, vol. 4, pp. 1-11, doi: 10.1186/1868-7083-4-20.

Attached Files
Name Description MIMEType Size Downloads
craig-genomescalecase-2012.pdf Published version application/pdf 1.20MB 1

Title Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease
Author(s) Ellis, Justine A
Munro, Jane E
Chavez, Raul A
Gordon, Lavinia
Joo, Jihoon E
Akikusa, Jonathan D
Allen, Roger C
Ponsonby, Anee-Louise
Craig, Jeffrey M
Saffery, Richard
Journal name Clinical epigenetics
Volume number 4
Article ID 20
Start page 1
End page 11
Total pages 11
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2012-11-13
ISSN 1868-7075
1868-7083
Keyword(s) epigenetics
juvenile idiopathic arthritis
DNA methylation
autoimmunity
methylome
methotrexate
science & technology
life sciences & biomedicine
oncology
Summary BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune disease. However, nothing is currently known about the potential role of aberrant DNA methylation in JIA. As a first step to addressing this knowledge gap, we have profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls. Genomic DNA was isolated from peripheral blood CD4+ T cells from 14 oligoarticular and polyarticular JIA cases with active disease, and healthy age- and sex-matched controls. Genome-scale methylation analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at >25,000 CpGs was compared in a case-control study design.

RESULTS: Methylation levels were significantly different (FDR adjusted p<0.1) at 145 loci. Removal of four samples exposed to methotrexate had a striking impact on the outcome of the analysis, reducing the number of differentially methylated loci to 11. The methotrexate-naive analysis identified reduced methylation at the gene encoding the pro-inflammatory cytokine IL32, which was subsequently replicated using a second analysis platform and a second set of case-control pairs.

CONCLUSIONS: Our data suggests that differential T cell DNA methylation may be a feature of JIA, and that reduced methylation at IL32 is associated with this disease. Further work in larger prospective and longitudinal sample collections is required to confirm these findings, assess whether the identified differences are causal or consequential of disease, and further investigate the epigenetic modifying properties of therapeutic regimens.
Language eng
DOI 10.1186/1868-7083-4-20
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, Ellis et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30110733

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 17 Abstract Views, 3 File Downloads  -  Detailed Statistics
Created: Tue, 10 Jul 2018, 10:54:19 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.