Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults

Aberrant DNA methylation in T cells has been linked to pathogenesis of autoimmune diseases. To investigate genomic and gene-specific DNA methylation levels in CD4(+) T cells from patients with latent autoimmune diabetes in adults (LADA), and to investigate changes in the expression of genes that regulate methylation as well as the autoimmune-related gene FOXP3 in these patients. Global CD4(+) T cell DNA methylation was measured in 15 LADA patients and 11 healthy controls using a methylation quantification kit. mRNA levels of DNA methytransferases (DNMTs), methyl-DNA binding domain proteins (MBDs) and FOXP3 were measured by real time PCR. Methylation of a FOXP3 regulatory element region was determined by bisulphite genomic sequencing. Genomic DNA methylation in CD4(+) T cells from LADA patients was significantly increased compared to controls. DNMT3b mRNA levels were higher in CD4(+) T cells from LADA patients than in controls. DNMT3b expression positively correlated with global DNA methylation in LADA CD4(+) T cells. FOXP3 expression was decreased, and the FOXP3 promoter region was hypermethylated in CD4(+) T cells from LADA patients compared with controls. DNA methylation levels are altered in CD4(+) T cells from LADA patients, which may contribute to disease onset and progression by affecting the expression of autoimmune-related genes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.