类风湿关节炎患者Ⅰ类干扰素效应基因表达的应用价值

Clinical implications of type I interferon signature gene expression in patients with rheumatoid arthritis

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qP CR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 subjects. 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（ q PCR） was used to detect the mRNA expression levels of MXA,MXB,IFIT1,IFIT2,ISG15,HERC5,Ly6E,RSAD2,EPSTRI1 and IFI35 genes. Serum 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 pretreatment than post-medication in RA patients（ P〈 0. 05）. Expression of IFIT2,ISG15,HERC5,MXA,MXB,Ly6E,RSAD2,EPSTRLI1 and IFI35 was significantly 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.