Aberrant Histone Modification In CD4+T Cells From Patients With Systemic Sclerosis

Objective:Systemic sclerosis (SSc) is a rare but devastating autoimmune disease. Nowadays, the pathogenesis of SSc is not clearly known. More and more studies show that epigenetics plays an important role in SSc. Our previous study proved that the global level of DNA methylation was abnormal in SSc CD4+T cells. The demethylation of regulatory genes(CD40L and CD70) contributes to their overexpression, which promotes T-B activation in SSc. So, we wonder whether histone modification, another epigenetic mechanism, is aberrant in SSc and whether this mechanism contributes to the pathogenesis of SSc.Methods:We obtained20SSc patients’and10normal controls’ CD4+T cells by density gradient centrifugation and MACS method. Then we investigated the differential levels of histone global H3/H4acetylation and H3K4/H3K9methylation by using EpiQuikTM global assay kit. The mRNA levels of associated HATs (p300,PCAF) and HDACs (HDAC1,2,3,4,6,7) were measured by Real-time PCR. Then according to the results, we did relative analysis between global H3acetylation and mRTSS value, its modified genes.Results:The levels of H3acetylation was remarkably reduced in CD4+T cells from SSc patients compared with the controls (P=0.015), and it was negatively related with mRTSS value. While the level of H4acetylation was increased in SSc patients with no significance(P=0.200). The mRNA levels of HATs(p300, PCAF) were upregulated in SSc patients(P=0.007,0.004). The mRNA levels of HDACs(HDAC1,HDAC4) were also distinctly increased in SSc patients(P=0.000,P=0.000), while HDACs(HDAC2, HDAC6, HDAC7) were remarkably decreased in SSc patients(0.000,0.000,0.005). And the expression level of HDAC1was negatively related with the level of histone global H3acetylation.Conclusion:The level of histone global H3acetylation in SSc patients was distinctly downregulated, and the modified genes of histone acetylation were differentially expressed. It suggests that histone modification is aberrant in SSc which may contribute to the pathogenesis of SSc.