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Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes
Author(s) -
Rhead Brooke,
Holingue Calliope,
Cole Michael,
Shao Xiaorong,
Quach Hong L.,
Quach Diana,
Shah Khooshbu,
Sinclair Elizabeth,
Graf John,
Link Thomas,
Harrison Ruby,
Rahmani Elior,
Halperin Eran,
Wang Wei,
Firestein Gary S.,
Barcellos Lisa F.,
Criswell Lindsey A.
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39952
Subject(s) - dna methylation , cpg site , methylation , rheumatoid arthritis , immunology , single nucleotide polymorphism , cd14 , medicine , epitope , genome wide association study , microbiology and biotechnology , biology , gene , genotype , genetics , antigen , immune system , gene expression
Objective To determine whether differentially methylated CpGs in synovium‐derived fibroblast‐like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples. Methods For this study, 371 genome‐wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells. Results Of 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single‐nucleotide polymorphisms from a genome‐wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA–DRB1 shared epitope risk allele and with a validated RA genetic risk score. Conclusion FLS‐representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status.