Genome-Wide Profiling in Treatment-Naive Early Rheumatoid Arthritis Reveals DNA Methylome Changes in T and B Lymphocytes

Abstract

Aims. Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease.

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes

“…The results of our study extend the recent findings demonstrating that DNA methylation profiles in PBMCs differ between RA patients and controls . While Glossop et al observed differences in both B lymphocytes and T lymphocytes , most results from the present study were confined to CD4+ naive T cells. However, taken together, the combined findings increase the evidence that PB cells contain a DNA methylation signature that can distinguish patients with RA from unaffected controls.…”

“…However, taken together, the combined findings increase the evidence that PB cells contain a DNA methylation signature that can distinguish patients with RA from unaffected controls. Furthermore, the DNA methylation profile differences detected in T cells of treatment‐naive patients in the study by Glossop et al suggest that there are methylation changes important in RA that are not a consequence of medication or long disease duration.…”

“…Liu et al studied global DNA methylation among 129 Taiwanese individuals and found that those with RA had significantly lower levels of DNA methylation in PBMCs compared to healthy control PBMCs . Recently, Glossop et al identified ∼2,000 differentially methylated CpGs in both T lymphocytes and B lymphocytes between treatment‐naive patients with early RA and healthy individuals, and in a separate analysis, they found that DNA methylation profiles in synovial fluid–derived fibroblast‐like synoviocytes (FLS) had similarities with the profiles in tissue‐derived FLS .…”

Stochastics of Cellular Differentiation Explained by Epigenetics: The Case of T‐Cell Differentiation and Functional Plasticity

“…Moreover, CD4 T cells from SLE patients display upregulated expression of TET2/3 enzymes, and increased 5hmC levels were found in the promoter regions of many immunerelated genes, in agreement with upregulated gene expression [82]. It appears that disease-associated changes in the genome-wide DNA methylation pattern are present as well in other autoimmune diseases including RA [83,84], Grave's disease [85] or Behc ßet's disease [86]. In addition to T cells, such alterations can also extend to B cells [83,84] or monocytes [86].…”

DNA methylation detection at single base resolution using targeted next generation bisulfite sequencing and cross validation using capillary sequencing

“…Extensive research and data generation from candidate gene approaches (Ullah et al, 2015;Lin et al, 2015), encyclopedia of DNA elements (ENCODE) consortium (ENCODE Project Consortium, 2012) and genome-wide DNA methylation profiling of diseased and healthy individuals in variety of cell types and tissues (Exner et al, 2015;Glossop et al, 2016;Fernandez-Santiago et al, 2015;Yang et al, 2009), identified genes that can be potential biomarkers for the discovery of prognostics, diagnostics and therapeutics targets. Identified differentially methylated regions from different gene loci with multiple CpG sites is validated and replicated in large samples for its sensitivity and specificity before the clinical use of a biomarker in disease prediction/progression or therapeutic intervention (Tetzner et al, 2009;Van Neste et al, 2012;Boers et al, 2016).…”