| ObjectiveAcquired Immune Deficiency Syndrome(AIDS)is a deadly disease caused by Human immunodeficiency virus(HIV)infection that invades the body’s immune system and cause human immune deficiency,is one of the public health problems that threaten the health of all mankind.HAART treatment can successfully inhibit the replication of HIV-1 virus in the body of AIDS patients and rebuild the immune function.However,about 15-30%of AIDS patients still fail to recover their CD4~+T cell levels after HAART treatment,which is called poor immune function reconstruction.At present,it is generally believed that the imbalance between the generation and destruction of CD4~+T cells is the main reason for the poor immune reconstitution.It has been shown that Caspase-1mediated pyrotosis is the main cause of death of CD4~+T cells in AIDS patients.Therefore,this study aims to explore the correlation of Caspase-1 mediated cell pyrotosis in the process of immune reconstruction in AIDS patients,which could provide theoretical basis for the search of new targeted therapy and drug development for the reconstruction of immune function in AIDS patients.MethodsWe collected the age,sex,BMI,route of infection,treatment regimen,duration of treatment,last CD4~+T cell count,baseline CD4~+T cell count,baseline CD8~+T cell count,baseline CD4/CD8 ratio,baseline WBC and other clinical information,and peripheral blood samples from the Immunological Responders(IRs),Immunological non-responders(INRs),and normal immune function(Control Group,CG)of HIV/AIDS patients.The m RNA relative expression levels of GSDMD,Caspase-1,IL-1βand IL-18 were detected by RT-q PCR,and the protein expression levels of GSDMD,Caspase-1,IL-1βand IL-18 were detected by ELISA.SPSS22.0 software was used for statistical analysis after all data were sorted out in Excel.Measurement data were expressed as mean±standard deviation(x±s),and statistics were performed by t-test analysis and one-way ANOVA.Counting data were statistically analyzed using the chi-square test.Graph Pad Prism 8 software was used for mapping.Results(1)Results of demographic data71 patients of HIV/AIDS form IRs,58 patients of HIV/AIDS from INRs,and 28 patients from CG were collected.There were 46 males and 12 females in the INRs,including 7 patients in 20-40 years old group,30 patients in 40-60 years old group,and 21 in 60-80 years old group.The last CD4~+T cell count was144.32±36.59 cells/μl.There were 40 males and 31 females in the IRs,including18 patients in 20-40 years old group,43 patients in 40-60 years old group,and 10in 60-80 years old group.The last CD4~+T cell count was 386.94±119.32cells/μl.There were 11 males and 17 females in the CG,including 5 patients in 20-40 years old group,10 patients in 40-60 years old group,and 13 in 60-80 years old group.The last CD4~+T cell count was 670.42±200.45cells/μl.There were statistically significant differences in age,sex composition and the last CD4~+T cell count among the three groups.Male patients in the INRs were significantly more than those in the IRs and CG,and the number of patients aged60-80 in the INRs was significantly more than that in the IRs(P<0.05).The last CD4~+T cell count in INRs was lower than that in IRs,and the last CD4~+T cell count in IRs was lower than that in CG(P<0.05).There was no significant difference in BMI,route of infection,treatment plan and duration of treatment among the three groups(P>0.05).At the baseline level of immune function,the baseline CD4~+T cell count was93.22±93.72 cells/μL in the INRs and 126.90±84.74 cells/μL in IRs,and the difference was statistically significant(P<0.05).There was no significant difference in baseline CD8~+T cell count,baseline CD4/CD8 ratio,and baseline WBC(P>0.05).(2)The expression of pyroptosis related indexes in INRsThe expression level of Caspase-1 m RNA in peripheral blood was 1.13±0.86,1.42±0.95 and 3.20±3.30 in the CG,IRs and INRs,respectively.The expression level of Caspase-1 protein in serum was 31.20±32.89,58.76±44.94 and76.59±36.86 in the CG,IRs and INRs,respectively.The expression level of peripheral blood Caspase-1 m RNA in the INRs was significantly up-regulated compared with IRs and CG(P>0.05),but there was no significant difference in the expression level between the IRs and CG(P<0.05).The expression level of Caspase-1 protein was increased successively among the CG,IRs and INRs(P<0.05).The m RNA expression level of GSDMD in peripheral blood was 1.26±0.79,1.41±0.77 and 1.97±1.24 in the CG,IRs and INRs,respectively.The expression level of GSDMD protein in serum was 30.95±7.09,34.13±6.76 and 38.86±19.04in the CG,IRs and INRs,respectively.The expression level of GSDMD m RNA in the INRs was significantly up-regulated compared with IRs and CG(P<0.05),but there was no significant difference in the expression level between the IRs and CG(P>0.05).There was no significant difference in the expression of GSDMD protein among the CG,IRs and INRs(P>0.05).The expression level of IL-18 m RNA in peripheral blood was 1.38±1.69,1.36±1.80 and 4.18±4.71 in the CG,IRs and INRs,respectively.The expression level of serum IL-18 protein was 299.34±107.98,275.46±158.37 and375.24±148.13 in the CG,IRs and INRs,respectively.The expression levels of IL-18 m RNA and protein in peripheral blood in the INRs were significantly up-regulated compared with the CG and IRs(P>0.05),but there was no significant difference between the CG and IRs(P<0.05).The m RNA expression level of IL-1βin peripheral blood was 1.49±1.48,2.98±3.58 and 5.31±4.69 in the CG,IRs and INRs,respectively.The expression level of IL-1βprotein in serum was 110.75±44.28,128.37±68.87 and153.84±89.25 in the CG,IRs and INRs,respectively.The expression levels of IL-1βm RNA and protein in peripheral blood in INRs were significantly increased compared with with the CG and IRs(P>0.05),but there was no significant difference between the expression levels in the CG and IRs(P<0.05).Conclusions(1)Elderly men are high risk group in INRs,and low baseline CD4~+T cells are a risk factor in INRs.(2)The expression level of GSDMD m RNA was significantly increased in the in INRs,suggesting the INRs was related to the level of pyroptosis in vivo.(3)The expression levels of Caspase-1 in peripheral blood were significantly increased in the INRs,suggesting that the abnormally activated pyroptosis level in INRs was mediated by Caspase-1.(4)The IL-18 and IL-1βwere significantly increased in the INRs suggesting that the level of inflammation induced by Caspase-1 is related to the INRs. |
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