Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome
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- Nezam Altorok
- University of Michigan, Ann Arbor, and University of Toledo Medical Center Toledo Ohio
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- Patrick Coit
- University of Michigan Ann Arbor
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- Travis Hughes
- University of Michigan Ann Arbor
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- Kristi A. Koelsch
- Oklahoma Medical Research Foundation Oklahoma City
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- Donald U. Stone
- University of Oklahoma Health Sciences Center Oklahoma City
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- Astrid Rasmussen
- Oklahoma Medical Research Foundation Oklahoma City
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- Lida Radfar
- University of Oklahoma Health Sciences Center Oklahoma City
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- R. Hal Scofield
- Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center Oklahoma City
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- Kathy L. Sivils
- Oklahoma Medical Research Foundation Oklahoma City
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- A. Darise Farris
- Oklahoma Medical Research Foundation Oklahoma City
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- Amr H. Sawalha
- University of Michigan Ann Arbor
抄録
<jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A genome‐wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age‐, sex‐, and ethnicity‐matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array, and the data were validated using bisulfite sequencing.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>LTA</jats:italic> (encoding lymphotoxin α). Other relevant genes, such as <jats:italic>CD247</jats:italic>, <jats:italic>TNFRSF25</jats:italic>, <jats:italic>PTPRC</jats:italic>, <jats:italic>GSTM1</jats:italic>, and <jats:italic>PDCD1</jats:italic>, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of <jats:italic>STAT1</jats:italic>, <jats:italic>IFI44L</jats:italic>, <jats:italic>USP18</jats:italic>, and <jats:italic>IFITM1</jats:italic>. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene <jats:italic>RUNX1</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>
収録刊行物
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- Arthritis & Rheumatology
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Arthritis & Rheumatology 66 (3), 731-739, 2014-02-25
Wiley