John R Glossop1,2, Richard D Emes3,4, Nicola B Nixon2, Jon C Packham2, Anthony A Fryer1, Derek L Mattey1,2, William E Farrell1. 1. Institute for Science & Technology in Medicine, Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK. 2. Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK. 3. School of Veterinary Medicine & Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK. 4. Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK.
Abstract
AIM: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA. PATIENTS & METHODS: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals. RESULTS: Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T lymphocytes, 113 sites in B lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease. CONCLUSION: Treatment-naive early RA patients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA.
AIM: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA. PATIENTS & METHODS: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RApatients and 11 healthy individuals. RESULTS: Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T lymphocytes, 113 sites in B lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease. CONCLUSION: Treatment-naive early RApatients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA.
Entities:
Keywords:
B lymphocyte; CpG; DNA methylation; Illumina 450K array; T lymphocyte; early rheumatoid arthritis; genome-wide; treatment naive
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