Abnormal DNA Methylation in T Cells from Patients with Subacute Cutaneous Lupus Erythematosus

Background: Impaired methylation of T-cell DNA is thought to contribute to the development of systemic lupus erythematosus. However, it is unknown whether T-cell hypomethylation is a factor in other, less severe, forms of lupus erythematosus such as subacute cutaneous lupus erythematosus (SCLE).

Objectives: To investigate global DNA methylation and the expression of genes that regulate methylation in T cells of patients with SCLE.

Methods: We quantified global methylcytosine levels in CD4+ and CD8+ T cells from 12 patients with SCLE and nine healthy controls. mRNA levels of DNA methyltransferases (DNMTs), methylated CpG binding proteins (MBDs) and CD11a were measured by real-time quantitative polymerase chain reaction.

Results: CD4+ T-cell DNA from patients with SCLE was hypomethylated relative to controls (P = 0.002). DNMT1 and DNMT3a mRNA levels were significantly lower in CD4+ T cells from SCLE patients than in controls (P = 0.027 and P = 0.004, respectively). Relative to controls, MBD1, MBD3 and MBD4 mRNA levels were significantly higher in SCLE CD4+ cells (P < 0.001, P < 0.001 and P = 0.001, respectively), whereas MECP2 and MBD4 mRNA expression were significantly increased in SCLE CD8+ T cells (P = 0.001 and P = 0.001, respectively). DNMT1 expression positively correlated with CD4+ T-cell DNA methylation within our SCLE patient cohort (r = 0.590, P = 0.044). CD11a mRNA expression was significantly increased in SCLE CD4+ T cells relative to controls (P = 0.044) and negatively correlated with DNA methylation (r = -0.669, P = 0.049).

Conclusions: These data suggest that aberrant regulation of DNA methylation in CD4+ T cells is associated with the development of SCLE.