期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 75, 期 5, 页码 933-940出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2014-206998
关键词
Sjogren's Syndrome; T Cells; B cells; Autoimmune Diseases; Autoantibodies
类别
资金
- French National Research Agency [ANR- 2010-BLAN-1133 01]
Background Beyond genetics, epigenetics alterations and especially those related to DNA methylation, play key roles in the pathogenesis of autoimmune diseases such as primary Sjogren's syndrome (pSS) and systemic lupus erythematosus. This study aimed to assess the role of methylation deregulation in pSS pathogeny through a genome-wide methylation approach. Patients and methods 26 female patients with pSS and 22 age-matched controls were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and their genome-wide DNA methylation profiles were analysed using Infinium Human Methylation 450K BeadChips. Probes with a median DNA methylation difference of at least 7% and p<0.01 between patients and controls were considered significantly differentially methylated. Results Methylation alterations were mainly present in B cells compared with T cells. In B cells, an enrichment of genes with differentially methylated probes in genetic at-risk loci was observed, suggesting involvement of both genetic and epigenetic abnormalities in the same genes. Methylation alterations in B cells were more frequent in some specific pathways including Interferon Regulated Genes, mainly among patients who were autoantibody positive. Moreover, genes with differentially methylated probes were over-represented in B cells from patients with active disease. Conclusions This study demonstrated more important deregulation of DNA methylation patterns in B cells compared with T cells, emphasising the importance of B cells in the pathogenesis of the disease. Overlap between genes with differentially methylated probes in B lymphocytes and genetic at-risk loci is a new finding highlighting their importance in pSS.
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