特发性炎性肌病外周血干扰素诱导基因表达与临床相关性研究

Expression of interferon inducible genes in peripheral blood of patients with idiopathic inflammatory myopathy and its clinical relevance analysis

目的 探讨Ⅰ型干扰素诱导基因（IFIG）在特发性炎性肌病（IIM）的表达及与临床特征相关性.方法 实时荧光定量PCR检测52例IIM患者及20名健康对照组PBMCs中6个代表性的IFIG-2＇,5＇-寡腺苷酸合成酶1（OAS-1）、三角形四肽重复干扰素诱导蛋白（IFIT）1、IFIT4、干扰素诱导蛋白（IFI）44、含蛋白2激进的S-腺苷甲硫氨酸域（RSAD2）和黏液病毒抗性蛋白1（MX-1）的mRNA水平,计算IFN积分,并与相应临床资料进行统计学分析.组间比较采用Mann-Whitney检验,相关性分析采用Spearman检验.结果 IIM组患者OAS-1基因[90.4（40.2,350.8）]、IFIT1基因[112.7（49.8,151.1）]、IFIT4基因[127.8（110.4,200.2）]、IFI44基因[100.3（39.5,160.7）]、RSAD2基因[100.9（50.2,559.2）]、MX-1基因[110.7（60.3,298.9）]的mRNA水平均明显高于健康对照组[分别为4.5（2.1,27.8）,21.5（0.4,31.4）,21.5（0.8,51.2）,5.2 （0.4,27.8）,27.8（17.5,33.5）,25.1（15.7,31.8）] （Z=-5.121,-4.359,-5.301,-4.906,-4.348,-4.151;P＜0.01）.与健康对照组[1.2（0.1,3.1）]比较,IFN积分在IIM患者中显著增高[65.7（3.6,136.9）,Z=-5.778,P＜0.01],尤其是伴有肺间质病变者[89.3 （41.9,176.7）] IFN积分高于非肺间质病变组[71.1（33.3,103.5）],Z=0.544,P＜0.05].IFN积分与ESR呈正相关（r=0.234,P＜0.05）.结论 OAS-1、IFIT1、IFIT4、IFI44、RSAD2和MX-1的mRNA水平在IIM患者中表达明显增高,IFN积分可能是反映IIM活动及肺部受累的生物学标志物.

Objective To explore the expression of interferon-inducible genes （IFIG） in idiopathic inflammatory myopathies （IIM） patients and its clinical significance.Methods Peripheral blood mononuclear cells from 52 IIM patients and 20 healthy controls were extracted.The transcriptional levels of six IFIG genes：oligoadenylate synthetase 1 （OAS-1）,IFN-induced protein with tetratricopeptide repeats 1（IFIT1）,IFIT4,interferon-inducible-protein 44 （IFI44）,radical S-adenosyl methionine domain containing protein 2 （RSAD2） and myxo-virus resistance gene 1 （MX-1） were detected by real-time polymerase chain reaction （PCR）.Interferon scores were calculated and compared.The correlations between interferon scores and clinical features of IIM patients were investigated.Non-parametric Mann-Whitney and Spearman analysis were used for statistical analysis.Results In IIM patients,the transcriptional levels of OAS-1 [90.4（40.2,350.8）],IFIT1 [112.7（49.8,151.1）],IFIT4 [127.8（110.4,200.2）],IFI44 [100.3（39.5,160.7）],RSAD2 [100.9（50.2,559.2）] and MX-1 [110.7（60.3,298.9）] were greatly higher than those in healthy controls [4.5（2.1,27.8）,21.5（0.4,31.4）i 21.5（0.8,51.2）,5.2（0.4,27.8）,27.8（17.5,33.5）,25.1（15.7,31.8）,respectively] （Z=-5.121,-4.359,-5.301,-4.906,-4.348,-4.151; P〈0.01）.Meanwhile,interferon scores were significantly elevated in IIM patients [65.7（3.6,136.9）,Z=-5.778,P〈0.01],compared with healthy controls [1.2（0.1,3.1）],especially in those with interstitial lung disease [89.3（41.9,176.7）,Z=0.544,P〈0.05].Interferon scores were correlated positively with ESR （r=0.234,P〈0.05）.Conclusion The mRNA levels of OAS-1,IFIT1,IFIT4,IFI44,RSAD2 and MX-1 are significantly increased in patients with IIM.Interferon score might be used as a new biomarker for IIM patients.