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MGAT3 and BACH2 promoter methylation correlates with the immunoglobulin G glycome in inflammatory bowel diseases

Inflammatory bowel diseases (IBD) represent a group of autoimmune diseases that occur due to aberrant immune response to intestinal microbiome in genetically susceptible individuals. Recent genome and epigenome-wide association studies have identified significant genetic and epigenetic changes in IBD. Genetic variants in the BACH2 and MGAT3 loci have been associated with both IBD and immunoglobulin G (IgG) glycosylation. We analysed CpG methylation in promoter regions of these genes from peripheral blood of IBD patients and healthy controls (HC) from two independent cohorts, using bisulfite pyrosequencing. We found significant differences in the methylation levels in BACH2 and MGAT3 between IBD patients and HC. The same pattern of methylation changes was also identified in CD19+ B cells from a subset of the IBD patients and HC. We also performed a correlation analysis between methylation and individual IgG glycans, measured in the same individuals. MGAT3 methylation correlated significantly with galactosylation, sialylation and bisecting GlcNAc on IgG, suggesting that activity of the enzyme encoded by this gene might be altered in IBD. Our results suggest that epigenetic deregulation of the MGAT3 gene might lead to an increase in proinflammatory properties of IgG in IBD through changes in IgG glycosylation

DNA methylation, BACH2, MGAT3, Immunoglobulin G, IBD

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