Abnormal histone modification patterns in lupus CD4+ T cells.

Abstract

To investigate alterations in histone modifications in patients with systemic lupus erythematosus (SLE). Global histone H3/H4 acetylation and H3K4/H3K9 methylation in CD4+ T cells from 20 SLE patients and 10 healthy control subjects were assayed using the EpiQuik global histone H3/H4 acetylation and H3K4/H3K9 methylation assay kits. mRNA levels of 12 members of 3 classes of chromatin modifier genes were measured by real-time quantitative polymerase chain reaction. Global histone H3 and H4 hypoacetylation was observed in active lupus CD4+ T cells compared with controls (p = 0.002 and p = 0.009, respectively). The degree of histone H3 acetylation correlated negatively with increased disease activity in lupus patients as measured by SLEDAI (r = -0.889, p = 0.044). We found global histone H3K9 hypomethylation in both active and inactive lupus CD4+ T cells, compared with controls (p = 0.001, p = 0.003, respectively). However, global levels of H3K4 methylation were not different between patients and controls. SIRT1 mRNA levels were significantly increased in active lupus CD4+ T cells compared with controls (p < 0.001), while mRNA levels of CREBBP, P300, HDAC2, HDAC7, SUV39H2, and EZH2 were significantly downregulated in patients with active lupus (p < 0.001, p < 0.001, p = 0.01, p < 0.001, p = 0.003, p = 0.001, respectively). Histone modifications appear abnormal in CD4+ T cells in SLE.