Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes

Epigenomics. 2016 Feb;8(2):209-24. doi: 10.2217/epi.15.103. Epub 2015 Nov 10.

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.

Keywords: B lymphocyte; CpG; DNA methylation; Illumina 450K array; T lymphocyte; early rheumatoid arthritis; genome-wide; treatment naive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / genetics*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Cluster Analysis
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*