title: Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  FLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status.
authors.affiliation: University of California, Berkeley.
authors.forename: Brooke
authors.initials: B
authors.lastname: Rhead
authors.affiliation: University of California, Berkeley.
authors.forename: Calliope
authors.initials: C
authors.lastname: Holingue
authors.affiliation: University of California, Berkeley.
authors.forename: Michael
authors.initials: M
authors.lastname: Cole
authors.affiliation: University of California, Berkeley.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Shao
authors.affiliation: University of California, Berkeley.
authors.forename: Hong L
authors.initials: HL
authors.lastname: Quach
authors.affiliation: University of California, Berkeley.
authors.forename: Diana
authors.initials: D
authors.lastname: Quach
authors.affiliation: University of California, San Francisco.
authors.forename: Khooshbu
authors.initials: K
authors.lastname: Shah
authors.affiliation: University of California, San Francisco.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.affiliation: University of California, San Francisco.
authors.forename: John
authors.initials: J
authors.lastname: Graf
authors.affiliation: University of California, San Francisco.
authors.forename: Thomas
authors.initials: T
authors.lastname: Link
authors.affiliation: University of California, San Francisco.
authors.forename: Ruby
authors.initials: R
authors.lastname: Harrison
authors.affiliation: Tel Aviv University, Tel Aviv, Israel.
authors.forename: Elior
authors.initials: E
authors.lastname: Rahmani
authors.affiliation: Tel Aviv University, Tel Aviv, Israel, and The International Computer Science Institute, Berkeley, California.
authors.forename: Eran
authors.initials: E
authors.lastname: Halperin
authors.affiliation: University of California at San Diego, La Jolla.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: University of California at San Diego, La Jolla.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Firestein
authors.affiliation: University of California, Berkeley.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.affiliation: University of California, San Francisco.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008875:Middle Aged; D000070918:Synoviocytes / Q000276:immunology*