Demethylation of promoter regulatory elements contributes to CD70 overexpression in CD4+ 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 (SLE). CD70 (TNFSF7) is a B-cell costimulatory molecule that contributes to excessive B-cell stimulation in vitro and in vivo. CD70 is overexpressed in CD4+ T cells of patients with SLE, and DNA demethylation occurs in promoter sequences that regulate CD70 expression in SLE CD4+ T cells. However, it is unknown whether the expression and methylation of CD70 in CD4+ T cells are affected in patients with subacute cutaneous lupus erythematosus (SCLE).

OBJECTIVE

To compare CD70 expression levels and the methylation status of the CD70 promoter region in CD4+ T cells from patients with SCLE and healthy controls.

METHODS

We used real-time RT-PCR to compare messenger RNA levels of CD70 and flow cytometry to compare CD70 protein levels in CD4+ T cells from patients with SCLE and healthy controls. Bisulphite sequencing was used to determine the methylation status of the CD70 promoter region.

RESULTS

CD70 is overexpressed at the surface of SCLE CD4+ T cells. Demethylation of the CD70 promoter region was seen in CD4+ T cells from patients with SCLE.

CONCLUSIONS

Demethylation of regulatory elements contributes to CD70 overexpression in CD4+ T cells of patients with SCLE.