Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis

Abstract

OBJECTIVES: T-cell DNA hypomethylation is thought to contribute to the development of systemic erythematosus lupus (SLE). However, it is unknown whether impaired T-cell DNA methylation occurs in other connective tissue diseases, such as systemic sclerosis (SSc) and dermatomyositis (DM). METHODS: We quantified global methylation in CD4+ T cells from 12 healthy donors and patients with SLE, SSc, and DM (10 patients in each group). mRNA levels of DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) were measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: CD4+ T-cell DNA from patients with SLE (both active and inactive) and SSc, but not DM, was significantly hypomethylated relative to controls. The average expression levels of DNMT1 and MBD4 mRNA were significantly lower whereas MBD2 and MeCP2 mRNA levels were significantly higher in the SLE group. DNMT1, MBD3, and MBD4 mRNA was significantly decreased in the SSc group, whereas MBD2 and MeCP2 mRNA was significantly higher in the DM group. The degree of global DNA hypomethylation correlated positively with the relative level of DNMT1 across SLE samples and MBD4 across the SSc samples. CONCLUSION: Reduced DNA methylation and abnormal expression of methylation-related genes in CD4+ T cells are associated with SLE and SSc.