The Study Of Serum Cholinesterase Level And Expression Of Non-Neuronal Cholinergic System Genes In Peripheral Mononuclear Cells Of Patients With Systemic Lupus Erythematosus

Objective:To investigate the correlation between serum cholinesterase level and disease activity of systemic lupus erythematosus,and the changes of serum ChE level in different organ involvement of SLE patients,to analyze the relevance between it and inflammatory cytokines and others laboratory index.To explore the differential expression of non-neuronal cholinergic system in peripheral blood mononuclear cells of SLE patients.Methods:(1)The clinical data and laboratory data of 210 SLE patients and 210 healthy controls(HC)were collected.SLE patients were divided into lupus nephritis group(LN group)and non-lupus nephritis group(non-LN group),serositis group and non □ serositis group,hematological abnormalities and non-hematological abnormalities.According to SLEDAI,SLE patients were divided into the active group and the remission group.All groups of serum ChE level were compared.Spearman correlation analysis was used to analyze correlation between serum ChE level and SLE activity.(2)The laboratory data of serum ChE and inflammatory cytokines in 44 patients with SLE were collected,and the correlation between serum ChE level and inflammatory cytokines was analyzed.(3)The blood of 60 SLE patients and 60 HC mached in age and sex were collected.Real-time PCR analysis the expression of choline acetyltransferase(choline acetyltransferase,ChAT)、acetylcholinesterase(acetylcholinesterase,AChE)、muscarinic acetylcholine receptor(mAChR)、nicotinic acetylcholine receptor(nAChR),mAChR subtypes contain M1R、M2R、M3R、M4R、M5R,nAChR subtypes contain α2、α3、α4、α5、α6、α7、α9、α10、β2、β3、β4).Results:(1)The of serum ChE level in the SLE patients was significantly lower than in the healthy control(P<0.001).Serum ChE level of SLE patients in the LN group was lower than that in the non□LN.The of Serum ChE level of SLE patients with serositis was lower than that in the group without serositis,with statistically significant differences(both P<0.001),and the of Serum ChE level of SLE patients with hematological abnormalities was lower than that in the group without hematological abnormalities,with statistically significant differences(P=0.001).The of serum ChE level in the active group was lower than those remissions group,with statistically significant differences(P<0.001).The of serum ChE level was negatively correlated with SLEDAI scores(r=-0.526,P<0.001).(2)The of serum ChE level was negatively correlated with IL-6、IL-10、IFN-γ,the rs value respectively were-0.325、-0.523、-0.385(both P<0.05),and there were no correlation serum ChE level and IL-2、IL-4、IL-17A、IFN-γ(both P>0.05).(3)The expression of MSmAChR and β2nAChR mRNA in PBMCs of SLE patients were higher than that of healthy controls(HC)(P<0.05).The expression of AChE and a6nAChR mRNA was lower than HC(P<0.05).There was no significant difference in ChAT、mAChR(MIR、M2R、M3R、M4R)、nAChR(α2、α3、α4、α5、α7、α9、α10、β3、β4)mRNA expression between SLE and HC(P>0.05)Conclusion:(1)The decrease of serum ChE level in SLE patients,it is related to SLE disease activity and organ or system involvement,it is suggested that it can be used as a new inflammatory marker and has important clinical significance in evaluating disease activity and organ involvement in patients with SLE.(2)There is an imbalance of inflammatory cytokines in patients with SLE,and the level of serum ChE is negatively correlated with IL-6,IL-10 and TNF-α,which may be due to the regulation of cholinergic level through related mechanisms to antagonize excessive secretion of inflammatory cytokines and systemic inflammatory response.(3)There were differences in the expression of AChE,M5mAChR,α6nAChR and β 2nAChRmRNA in PBMCs of SLE patients.It is suggested that non-neuronal cholinergic system is related to the pathogenesis of SLE.