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. 2013 Mar:41:175-81.
doi: 10.1016/j.jaut.2013.02.002. Epub 2013 Mar 7.

Epigenetic dysregulation in salivary glands from patients with primary Sjögren's syndrome may be ascribed to infiltrating B cells

Yosra Thabet  1 , Christelle Le Dantec, Ibtissem Ghedira, Valérie Devauchelle, Divi Cornec, Jacques-Olivier Pers, Yves Renaudineau
Affiliations

Epigenetic dysregulation in salivary glands from patients with primary Sjögren's syndrome may be ascribed to infiltrating B cells

Yosra Thabet et al. J Autoimmun. 2013 Mar.

Abstract

Sjögren's syndrome (SS) is an autoimmune exocrinopathy characterized by an epithelium injury with dense lymphocytic infiltrates, mainly composed of activated T and B cells. Present at the interface of genetic and environmental risk factors, DNA methylation is suspected to play a key role in SS. To clarify this point, global DNA methylation was tested within salivary gland epithelial cells (SGEC), peripheral T cells and B cells from SS patients. Global DNA methylation was reduced in SGEC from SS patients, while no difference was observed in T and B cells. SGEC demethylation in SS patients was associated with a 7-fold decrease in DNA methyl transferase (DNMT) 1 and a 2-fold increase in Gadd45-alpha expression. The other DNA methylation/demethylation partners, tested by real time PCR (DNMT3a/b, PCNA, UHRF1, MBD2, and MBD4), were not different. Interestingly, SGEC demethylation may be attributed in part to the infiltrating B cells as suspected in patients treated with anti-CD20 antibodies to deplete B cells. Such hypothesis was confirmed using co-culture experiments with human salivary gland cells and B cells. Furthermore, B cell-mediated DNA demethylation could be ascribed to an alteration of the PKC delta/ERK/DNMT1 pathway. As a consequence, part of the SGEC dysfunction in SS may be linked to epigenetic modifications, thus opening new therapeutic perspectives in SS.

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