类风湿关节炎患者Ⅰ类干扰素效应基因表达的应用价值

摘要

目的:检测类风湿关节炎(RA)患者和正常对照组Ⅰ类干扰素(IFN)效应基因mRNA的表达,探讨IFN在RA发病过程中的意义.方法:收集32例RA患者和健康体检人群,分为治疗前RA组、治疗后RA组和正常对照组,患者均为首次就诊或未使用改变病情抗风湿药,留取全血,采用qPCR方法检测MXA、MXB、IFIT1、IFIT2、ISG15、HERC5、Ly6E、RSAD2、EPSTRI1、IFI44L、IFI35和IFI6基因mRNA的表达,检测血清抗CCP抗体和RF,比较mRNA组间基因表达差异及与自身抗体水平相关性.结果:IFIT1、ISG15、HERC5、MXA、MXB、Ly6E和RSAD2在治疗前RA患者组中的mRNA表达水平高于治疗后RA组(P<0.05),IFIT2、ISG15、HERC5、MXA、MXB、Ly6E、RSAD2、EPSTRLI1和IFI35在治疗前RA组中mRNA的表达水平均高于正常对照组(P<0.05),ISG15、HERC5、RSAD2在治疗后RA组中mRNA的表达水平均高于正常对照组(P<0.05).IFI6、IFIT2、IFI35、ISG15、MXB、Ly6E、EPSTRI1和MXA的mRNA的表达水平与抗CCP抗体呈正相关性(r=0.354~0.667,P<0.05),IFI6、IFIT2、IFI35、MXB、Ly6E、和MXA的mRNA的表达水平与RF呈正相关(r=0.362~0.579,P<0.05).结论:RA患者炎症细胞IFN效应基因mRNA表达升高,表明IFN可能是RA自身免疫反应的诱发因素.%Objective:To investigate the implications of typeⅠInterferon( IFN) signature gene expression in patients with rheumatoid arthritis( RA) in different dates of disease.Methods:Blood samples were collected from 32 RA patients(first diagnosis without use of antirheumatic drugs) and healthy sub-jects.RA patients were divided into pre-RA treatment group and post-treatment group,and the healthy subjects were included in control group.Real-Time PCR (qPCR) was used to detect the mRNA expression levels of MXA,MXB,IFIT1,IFIT2,ISG15,HERC5,Ly6E,RSAD2,EPSTRI1 and IFI35 genes.Se-rum anti-cyclic citrullinated peptide antibody(anti-CCP) and rheumatoid factor(RF) concentrations were also measured to compare their correlation with expression of the signature genes described above.Results:The mRNA expression IFIT1,ISG15,HERC5,MXB,Ly6E and RSAD2 genes was higher in pre-treatment than post-medication in RA patients(P<0.05).Expression of IFIT2,ISG15,HERC5,MXA,MXB,Ly6E,RSAD2,EPSTRLI1 and IFI35 was sig-nificantly higher in patients in pre-RA treatment group than that of the controls ( P<0.05) ,whereas mRNA expression in ISG15,HERC5 and RSAD2 was higher in patients following treatment than that of control group (P<0.05).Expression of MXA,MXB,IFIT2,ISG15,EPSTRI1,IFI6,Ly6E and IFI35 genes was positively correlated with the serum level of anti-CCP (r=0.354-0.667;P<0.05).Likewise,gene expression of IFI6,IFIT2,IFI35,MXB,Ly6E and MXA demonstrated a similar relationship with RF(r=0.362-0.579,P<0.05).Conclusion:Up-regulated mRNA expression in the INF signature genes was seen RA patients,suggesting that INF may be precipitating factors in autoimmune response in patients with RA.