The Expression And Significance Of IRF-1 In Systemic Lupus Erythematosus

Object:Systemic lupus erythematosus(SLE)which characterized by B cell hyperactivity leading to excessive production of autoantibodies,is a severe systemic autoimmune disease.The accurate etiology of SLE is still unknown.Excessive production of residual antigen-antibody immune complex leads to the response of type I interferons(IFNs)and the activation of dendritic cell(DC),which is most suspected to play a central role in SLE.Interferon regulatory factors-1(IRF-1)is the first number of IFN regulatory factor,plays an important role in many autoimmune diseases.Our study is to investigate the expression and significance of IRF-1 on peripheral mononuclear cells(PBMC),CD4~+T and CD8~+T lymphocyte subsets in patients with SLE.Methods:Part one:25 patients with newly-onset SLE and 25 normal healthy controls(HC)matched for gender and age were recruited,their clinical data had also been collected.Peripheral blood was collected by anti-coagulated tube and PBMCs were isolated.IRF-1 mRNA expression of PBMC was quantized by real-time polymerase chain reaction(Real-time PCR).IRF-1mRNA expression levels was compared in patients with HC and SLE.The correlation was analyzed between the relative expression of IRF-1 mRNA and clinical indices by Pearson correlation analysis.Part two:35 SLE patients and 25 HC matched for gender and age were recruited.Clinical data was collected.CD4~+T cells were enriched and the IRF-1mRNA expression was analyzed.The level of plasma Th1 cytokine IL-12 was detected by ELISA.The correlation was analyzed between expression of IRF-1and IL-12.At the same time,the correlation analysis between expressions of IRF-1 and IL-12 and clinical indices was done.Part three:10 SLE patients and 8 HC matched for gender and age were recruited.Clinical data was collected.CD8~+T cells were enriched and the IRF-1mRNA expression was analyzed.The correlation analysis between expression of IRF-1 and clinical indices was done.Results:1.The expression level of IRF-1mRNA in PBMCs from SLE patients is significantly down-regulated compared with that from human control(p<0.01).No significant correlation was observed between expression of IRF-1 and disease activity as determined by SLEDAI score,laboratory examination including the serum C3,C4 level,titters of anti-dsDNA antibody,etc(P>0.05).There is no significant differences of expression of IRF-1 between the clinical group and comparative group(P>0.05).2.The expression level of IRF-1mRNA in CD4~+T cells from SLE patients is also down-regulated compared with that from HC(p<0.05).No significant correlation were found between expression of IRF-1 and SLEDAI score,laboratory examination(P>0.05).There is no significant differences of expression of IRF-1 between the clinical group and comparative group(P>0.05).3.Plasma level of Th1 cytokine IL-12 in SLE patients is lower than HC(p<0.05),and is positively correlated with SLEDAI(r=0.421,P=0.008),but inversely correlated with C4(r=-0.439,P=0.007).4.The expression level of IRF-1mRNA in CD4~+T cells is positively correlated with plasma level of IL-12(r=0.644,P=0.001);However,no significant correlation were found between expression of IRF-1 in PBMC and IL-12(r=0.46,P=0.07).5.In CD8~+T cells,the expression level of IRF-1mRNA from SLE patients is significantly down-regulated compared with that from HC(p<0.01).Expression of IRF-1 on CD8~+T cells is positively correlated with CD8~+T cells ration(r=0.75,P=0.02).No significant correlation were found between expression of IRF-1 and SLEDAI score,other laboratory examination(P>0.05).There is no significant differences of expression of IRF-1 between the clinical group and comparative group(P>0.05).Conclusions:The expression of IRF-1mRNA in PBMCs,CD4+T cells and CD8+T cels significantly decrease in SLE patients.SLE patients'plasma Th1 cytokine IL-12 in is positively correlated with the expression of IRF-1in CD4+T cells.Expression of IRF-1 on CD8~+T cells is also positively correlated with CD8~+T cells ration.Therefore,IRF-1 might be regarded as one of the potential factors during SLE occurrence and development by regulating production and differentiation of CD8~+T cells and/or Th1 cells and its cytokine IL-12.