Modulation of Histone Deacetylases (HDACs) Expression in Patients with and without Systemic Lupus Erythematosus: Possible Drug Targets for Treatment

Abstract

There is increasing evidence that epigenetic factors may play a role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Both global and gene specific methylation is known to occur in lupus patients, as well as, changes in histone acetylation status. Histone acetylation is associated with active chromatin or activation of genes, whereas histone deacetylase (HDAC) activity is associated with silencing of genes. Therefore, HDACs have been targeted as potential therapeutic targets for a number of diseases, including lupus. The purpose of this study was to determine histone deacetylase (HDAC) expression in patients who are diagnosed with SLE compared to age-matched healthy controls. Quantitative real-time PCR expression levels of HDAC 1, HDAC 2 and HDAC 7 were investigated in peripheral blood mononuclear cells of African American and European American women. Our results showed that HDAC 1 expression is significantly (p < 0.0039) elevated in lupus patients compared to controls. HDAC 2 expression is also increased in lupus patients (p < 0.0427). However, HDAC 7 showed no significant difference (p < 0.4644) in expression in our SLE patients compared to their controls. Those lupus patients with a SLE disease activity index (SLEDAI) of 4 or greater showed lower expression of HDAC 1 (p < 0.0026) compared to those with modest disease and a SLEDAI of less than 4. However, in those lupus patients with a SLEDAI of 4 or greater showed increased expression of HDAC2 (p < 0.053) when compared to those with a SLEDAI of less than 4. This observation was also noted in HDAC7. Increased expression in HDAC 1 and 2 has been associated with induced kidney injury and induction of proinflammatory cytokines.