The contribution of epigenetics in Sjögren's Syndrome

Abstract

Sjögren's syndrome (SS) is a chronic autoimmune epithelitis that combines exocrine gland dysfunctions and lymphocytic infiltrations. While the pathogenesis of SS remains unclear, its etiology is multifunctional and includes a combination of genetic predispositions, environmental factors, and epigenetic factors. Recently, interest has grown in the involvement of epigenetics in autoimmune diseases. Epigenetics is defined as changes in gene expression, that are inheritable and that do not entail changes in the DNA sequence. In SS, several epigenetic mechanisms are defective including DNA demethylation that predominates in epithelial cells, an abnormal expression of microRNAs, and abnormal chromatin positioning-associated with autoantibody production. Last but not least, epigenetic modifications are reversible as observed in minor salivary glands from SS patients after B cell depletion using rituximab. Thus epigenetic findings in SS open new perspectives for therapeutic approaches as well as the possible identification of new biomarkers.

Keywords: DNA methylation; HERV; Sjögren’s syndrome; epithelial cells; microRNAs.

FIGURE 1

Chromatin. Nucleosomes are the repetitive unit in chromatin consisting of 145 bp of DNA wrapped around an octamer of histones. Charges on the histones are shown as blue (positive), red (negative), and white (neutral). The positive charges of histones facilitate binding to negatively charged DNA and thereby packaging the DNA to reduce the overall volume needed for the chromatin. Euchromatin is an extended form of chromatin that allows access to the underlying genes. Heterochromatin is a condensed form with histone H1 (orange) bound to the linker DNA between nucleosomes. This can compact the chromatin further and sequesters the underlying genes. The chromatin is further organized into loops that are usually tightly coiled and stacked into chromosomes but the loops can rapidly uncoil into extended states as depicted to allow access to sequestered genes.