TY - JOUR
T1 - Genome-wide DNA methylation patterns in naive cd4+ t cells from patients with primary sjögren's syndrome
AU - Altorok, Nezam
AU - Coit, Patrick
AU - Hughes, Travis
AU - Koelsch, Kristi A.
AU - Stone, Donald U.
AU - Rasmussen, Astrid
AU - Radfar, Lida
AU - Scofield, R. Hal
AU - Sivils, Kathy L.
AU - Farris, A. Darise
AU - Sawalha, Amr H.
PY - 2014/3
Y1 - 2014/3
N2 - Objective: Primary Sjögren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS. Methods: A genome-wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age-, sex-, and ethnicitymatched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation 450 BeadChip array, and the data were validated using bisulfite sequencing. Results: Genome-wide analyses identified 553 hypomethylated CpG sites and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with primary SS as compared to healthy controls, representing 311 hypomethylated and 115 hypermethylated gene regions. The hypomethylated genes in patients with primary SS included LTA (encoding lymphotoxin α). Other relevant genes, such as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18, and IFITM1. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. Conclusion: This is the first epigenome-wide DNA methylation study in patients with primary SS. These findings highlight a role for DNA methylation in primary SS and identify disease-associated DNA methylation changes in several genes and pathways in naive CD4+ T cells from patients with primary SS that may be involved in the pathogenesis of this disease.
AB - Objective: Primary Sjögren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS. Methods: A genome-wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age-, sex-, and ethnicitymatched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation 450 BeadChip array, and the data were validated using bisulfite sequencing. Results: Genome-wide analyses identified 553 hypomethylated CpG sites and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with primary SS as compared to healthy controls, representing 311 hypomethylated and 115 hypermethylated gene regions. The hypomethylated genes in patients with primary SS included LTA (encoding lymphotoxin α). Other relevant genes, such as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18, and IFITM1. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. Conclusion: This is the first epigenome-wide DNA methylation study in patients with primary SS. These findings highlight a role for DNA methylation in primary SS and identify disease-associated DNA methylation changes in several genes and pathways in naive CD4+ T cells from patients with primary SS that may be involved in the pathogenesis of this disease.
UR - http://www.scopus.com/inward/record.url?scp=84896266991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896266991&partnerID=8YFLogxK
U2 - 10.1002/art.38264
DO - 10.1002/art.38264
M3 - Article
C2 - 24574234
AN - SCOPUS:84896266991
SN - 2326-5191
VL - 66
SP - 731
EP - 739
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 3
ER -