Aberrant epigenetic modifications in peripheral blood mononuclear cells from patients with pemphigus vulgaris

摘要

Background Pemphigus vulgaris (PV) is an autoimmune blistering disorder with a complex aetiology involving genetic and environmental factors, most of which remain unknown. It has become increasingly evident that aberrant epigenetic modifications are associated with the occurrence and development of autoimmune skin disorders. However, it is not known whether epigenetic modifications play a role in the development of PV. Objectives To analyse DNA methylation and histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with PV. Methods PBMC samples were isolated from 24 patients with PV and 20 healthy controls. Skin lesion biopsies and control skin specimens were obtained from 25 patients with PV and 15 healthy controls. Global DNA methylcytosine levels, as well as histone acetylation and methylation levels, were measured by enzyme-linked immunosorbent assay. mRNA expression levels were determined using real-time reverse transcription-polymerase chain reaction. Results Genomic DNA methylation in PBMCs of patients with PV was increased relative to controls. DNMT1 expression levels were significantly higher in PV PBMCs than in controls. MBD3 expression was repressed in PV PBMCs compared with healthy controls. Global histone H3/H4 acetylation and H3K4/H3K27 methylation levels were significantly decreased in patient PBMCs compared with healthy controls. These changes were accompanied by increased HDAC1, HDAC2 and SUV39H2 and decreased SUV39H1 and EZH2 in PV PBMCs. Conclusions Aberrant DNA methylation and histone modifications occur in PBMCs of patients with PV, possibly due to the deregulation of epigenetic modifier genes. These changes may contribute to the pathological immune responses in PV.