Background and aims A lot of evidences have confirmed that genomic DNA hypomethylation play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of DNA hypomethylation in lupus CD4+ T cells remain unclear. Previous study showed that depletion of the mammalian siderophore by inhibiting expression of 3-OH butyrate dehydrogenase (BDH2) results in abnormal accumulation of intracellular iron and mitochondrial iron deficiency in cultured mammalian cells. In this study, we investigate whether BDH2 is involved in regulating DNA hypomethylation in CD4+ T cells of SLE.

Methods 20 SLE patients and 20 healthy controls were recruited. CD4+ T cells were isolated by magnetic beads. All patients fulfilled at least 4 of the SLE classification criteria of ACR. mRNA and protein levels were detected by real-time PCR and western blot. Global DNA methylation level was measured by Global DNA Methylation Assay–LINE-1 kit. CD4+ T cells were transfected by nucleofector.

Results Compared with normal controls, BDH2 mRNA and protein levels were decreased significantly in SLE CD4+ T cells, which are positively correlated with the global DNA methylation levels. Knockdown of BDH2 with siRNA in normal CD4+ T cells decreased the global DNA methylation level compared with negative control. In contrast, overexpressing BDH2 with expression plasmid can increase the global DNA methylation level in SLE CD4+ T cells.

Conclusions BDH2 expression was defect in CD4+ T cells of SLE patients, which contributes to the genomic DNA hypomethylation of CD4+ T cells in SLE patients.