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.