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

Content Provider	Springer Nature : BioMed Central
Author	Ellis, Justine A Munro, Jane E Chavez, Raul A Gordon, Lavinia Joo, Jihoon E Akikusa, Jonathan D Allen, Roger C Ponsonby, Anne-Louise Craig, Jeffrey M Saffery, Richard
Abstract	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.
Related Links	https://clinicalepigeneticsjournal.biomedcentral.com/counter/pdf/10.1186/1868-7083-4-20.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	18687083
DOI	10.1186/1868-7083-4-20
Journal	Clinical Epigenetics
Issue Number	1
Volume Number	4
Language	English
Publisher	BioMed Central
Publisher Date	2012-11-13
Access Restriction	Open
Subject Keyword	Human Genetics Gene Function Epigenetics Juvenile idiopathic arthritis DNA methylation Autoimmunity Methylome Methotrexate
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Genetics (clinical) Developmental Biology Genetics
Journal Impact Factor	4.8/2023
5-Year Journal Impact Factor	5.8/2023

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