Recent evidence indicates that human lupus is an epigenetic disease characterized by impaired T cell DNA methylation. Perforin, a cytotoxic effector molecule, is overexpressed due to hypomethylation of its promoter regulatory elements in CD4(+) T cells from patients with systemic erythematosus lupus (SLE). However, it is unknown whether aberrant expression and methylation of perforin occur in CD4(+) T cells from patients with subacute cutaneous lupus erythematosus (SCLE).We aimed to compare the perforin expression level and the methylation status of the perforin promoter region in CD4(+) T cells from SCLE patients and healthy controls.We used real-time RT-PCR to compare the perforin mRNA levels, and Western-blot to compare perforin protein levels in CD4(+) and CD8(+) T cells from SCLE patients and healthy controls. Bisulfite sequencing was used to determine the methylation status of the perforin promoter region.Perforin is overexpressed in SCLE CD4(+) T cells. Demethylation of the perforin promoter region was seen in CD4(+) T cells from patients with SCLE.DNA demethylation at the perforin locus contributes to perforin overexpression in SCLE CD4(+) T cells.