The Research On The Histone Acetylation In Peripheral Blood Mononuclear Cells Of Patients With Sjogren’s Syndrome

OBJECTIVE:Sjogren’s syndrome(SS)is an autoimmune disease mainly involving exocrine glands.It is mainly characterized by lymphocyte infiltration in exocrine glands and detection of various autoantibodies in serum.The pathogenesis of pSS is still unclear.It is currently believed that the disease is caused by a variety of environmental factors and intrinsic antigens on the basis of susceptibility genes,resulting in abnormal immune responses,destruction of exocrine glands,and damage to target organs[1,2].Reversible acetylation modifications play an important role in the regulation of immune responses.Some researchers have found that TNF-a inhibits the expression of aquaporin 5 in the glandular epithelial membrane by inhibiting histone H4 acetylation,and destroys the glandular acinar structure of pSS patients,resulting in glandular secretion reduce[3].This study focused on the level of histone acetylation in PBMCs of patients with pSS,to identify if there is an imbalance and explore its relevance to pSS.METHODS:We collected 46 patients diagnosed with pSS and 46 HCs peripheral blood.All patients met the 2016 ACR/EULAR pSS classification criteria.After PBMCs extraction,we used qPCR to detect the mRNA expression of HDACs(1-10)and HATs(P300,PCAF,CREBBP).The total HDACs and HATs activities were detected by elisa and the level of acetyl-histones H3 and acetyl-histones H4 were detected by western blot,flow cytometry,elisa,and analyzed the correlation between HATs activity and inflammation index.RESULTS:The expression of HATs and HDACs in mRNA decreased,and HATs enzyme activity decreased;the levels of acetyl-histones H3 and acetyl-histones H4 were significantly lower than those of HC.In flow cytometry,we found that the level of acetyl-histones H3 in T cells was significantly decreased,and there was no difference in histone H4 acetylation level.The HATs activity were negatively correlated with CRP,TNF-a and were positively correlated with C3,C4;negatively correlated with ESR,IgG,IgA,IgM also,but not statistically significant.CONCLUSION:This study showed that the level of histone acetylation was reduced and there was an imbalance of acetylation status in PBMCs of patients with pSS,which was associated with pSS patient’s disease activity.The imbalance of histone acetylation regulation may be involved in the pathogenesis of pSS.