Overlap between differentially methylated DNA regions in blood B lymphocytes and genetic at-risk loci in primary Sjögren's syndrome
Abstract
Background Beyond genetics, epigenetics alterations
and especially those related to DNA methylation, play
key roles in the pathogenesis of autoimmune diseases
such as primary Sjögren’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 450 K 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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