@Article{ecn.2012.0316,
AUTHOR = {Nicolas Gestermann, Mikael Koutero, Rakiba Belkhir, Jörg Tost, Xavier Mariette, Corinne Miceli-Richard},
TITLE = {Methylation profile of the promoter region of IRF5 in primary Sjögren’s syndrome},
JOURNAL = {European Cytokine Network},
VOLUME = {23},
YEAR = {2012},
NUMBER = {4},
PAGES = {166--172},
URL = {http://www.techscience.com/ECN/v23n4/65691},
ISSN = {1952-4005},
ABSTRACT = {The transcription factor interferon regulatory factor 5 (IRF5), in the type I interferon pathway is
involved in the genetic susceptibility to various autoimmune diseases. A 5-bp insertion/deletion (CGGGG indel)
polymorphism in the promoter region of IRF5 associated with primary Sjögren’s syndrome (pSS) could be epigenetically
deregulated in this condition. Therefore, we investigated DNA methylation patterns of the promoter region
of IRF5 to determine whether its epigenetic deregulation could explain the increased expression of IRF5 mRNA in
pSS patients, along with the risk of pSS induced by the genetic polymorphism. DNA extracted from total peripheral
blood mononuclear cells, isolated CD4<sup>+</sup> T cells, B lymphocytes and monocytes from 19 pSS patients and 24
healthy controls underwent methylation analysis by pyrosequencing. Salivary gland epithelial cells (SGECs) were
cultured from minor salivary glands. Regions of interest in the CGGGG repeat and ATG initiation codon region
were amplified by PCR and analysed by pyrosequencing. The effect of the demethylating agent 5-AzaC on IRF5
mRNA expression in controls was quantified by RT-PCR. Among the healthy controls, the mean methylation of the
nine CpG pairs of the CGGGG repeat region and the 18 CpG pairs of the ATG region was < 15% in CD4<sup>+</sup> T cells,
B lymphocytes, monocytes and SGECs. Patients and controls did not differ in methylation profiles as regards CD4<sup>+</sup>
T cells and B lymphocytes. IRF5 mRNA expression did not differ with or without 5-AzaC in controls. The absence
of aberrant DNA methylation profiles for the putative regulatory regions of IRF5 in CD4<sup>+</sup> T cells, B lymphocytes,
and monocytes from patients with pSS, does not support the hypothesis that epigenetic deregulation in combination
with the genetic polymorphism explains the increase in IRF5 mRNA levels in pSS patients.},
DOI = {10.1684/ecn.2012.0316}
}