系统性红斑狼疮患者干扰素诱导基因的表达及其与疾病活动陛的相关性研究

Expressions of interferon-inducible genes in patients with systemic lupus erythematosus and their assoc-iation with disease activity

目的探讨系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMCs）中5个干扰素（IFN）诱导基因（IFIT1、IFIT4、OAS1、OASL、ISG15）的表达及其与SLE疾病活动度的相关性。方法运用SYBRgreendveI实时定量聚合酶链反应（RT—PCR）方法检测76例SLE患者与54名健康对照人的IFIT1、IFIT4、OASI、OASL及ISG15 mRNA表达水平（以-△△Ct值表示），并且与红细胞沉降率（ESR）、C反应蛋白（CRP）、补体C3、C4、抗核抗体（ANA）及抗dsDNA抗体等指标比较，分析IFIT1、IFIT4、OAS1、OASL、ISG15mRNA表达水平以及上述常规检测指标与SLE疾病活动指数（SLEDA1）积分之间的相关性。结果①SLE组与正常对照组相比，IFIT1、IFIT4、OAS1、OASL及ISG15mRNA表达显著增高（P〈0．01）；SLE活动组与SLE缓解组比较，IFIT1、IFIT4、OAS1、OASL及ISG15 mRNA表达增高（P〈0．05）；SLE组IFIT1、IFIT4、OAS1、OASL及ISG15 mRNA表达水平之间呈正相关（r〉0．5，P〈0．05）。@SLE组IFITl、IFIT4、OASl、OASL及ISGl5mRNA表达水平均与SLEDAI积分呈显著正相关（r〉0．5，P〈0．05）。③ESR、CRP、补体c3、C4、ANA与IFIT1、IFIT4、OAS1、OASL、ISG15m RNA表达水平及SLEDAI积分均无相关性，抗dsDNA抗体与IFIT1、IFIT4、OAS1、OASL、ISG15 mRNA表达水平及SLEDAI积分呈正相关（r〉0．5，P〈0．05）。结论SLE患者IFIT1、IFIT4、OAS1、OASL及ISG15的表达水平在SLE患者中显著增高，并且与SLEDA1积分呈显著正相关，对SLE患者病情活动度和病情严重度的判断均有较大价值，抑制这5个基因的表达可能为SLE的治疗提供新的靶点。

Objective To investigate the expression levels of interferon-inducible genes （IFIT1, 1FIT4, OAS1, OASL, ISG15） in the peripheral blood mononuelear cells （PBMCs） of patients with systemic lupus erythematosus （SLE）, and the relations between these genes expression levels and disease activity are explored. Methods Sybr green dye based real-time quantitative PCR method was used to detect the expression levels （indicated as -△△Ct value） of IFIT1, IFIT4, OAS1, OASL and ISG15 in 76 patients with SLE and 54 controls. Their expression levels were compared with erythrocyte sedimentation rate （ESR）, serum C reactive protein （CRP）, complement C3, C4, antinuclear antibody （ANA）, anti-double stranded DNA antibody. The associations between the expression levels of IFIT1, IFIT4, OAS1, OASL, ISG15, ESR, CRP, complement C3, C4, ANA, anti-double stranded DNA antibody and SLEDAI scores in patients with SLE were analyzed. Results①The expression levels of IFIT1, IFIT4, OAS1, OASL and ISG15 in the SLE patients were significantly higher than those of the normal controls （P〈0.01）. The expression levels of IFIT1, IFIT4, OAS1, OASL and ISG15 in active SLE patients were higher than those of inactive SLE patients （P〈 0.05）. The real time expression levels of IFIT1, IFIT4, OAS1, OASL and ISG15 showed positive correlations with each other （r〉0.5, P〈0.05） in patients with SLE. ② The expression levels of IFIT1, IFIT4, OAS1, OASL and ISG15 were positively correlated with the SLEDAI scores （r〉0.5, P〈0.05）. ③There was no correlation between ESR, CRP, complement C3, C4, ANA and the expression levels of IFIT1, IFIT4, OAS1, OASL, ISG15, SLEDA1 scores except anti-double stranded DNA antibody （r〉0.5, P〈0.05）. Conclusion The expression levels of IFIT1, IFIT4, OAS1, OASL and ISG15 in patients with SLE are significantly higher than those of the normal controls, and positively associated with SLEDAI scores, so they are helpful in evaluating SLE disease activity and severity. IFIT1, IFIT4, OAS1, OASL and ISG15 genes may be the potential treating targets for SLE.