多发性肌炎／皮肌炎患者干扰素表达及与临床的相关性

Expression of interferon and its correlation with clinical features in idiopathic inflammatorymyopathies

目的研究多发性肌炎（PM）／皮肌炎（DM）患者干扰素（IFN）α、IFNβ、IFNγ,表达水平及其与肌病的临床关系，以探讨IFN在IIM发病中的作用。方法用酶联免疫吸附试验（EKISA）方法检测血清79例PM／DM患者（均来自2008年1月到2010年10月北京中日友好医院风湿免疫科）IFNα、IFNβ、IFNγ、抗组氨酰tRNA合成酶抗体（抗Jo-1抗体）。实时定量PCR法检测患者肌肉组织IFNα、IFNβ、干扰素α受体1（IFNαRl）、信号传导蛋白和转录激活物（STATl）的mRNA表达水平。结果PM／DM患者外周咂IFNtx（50±21）ng／L、IFNβ（10．7±5．4）ng／L表达明显高于正常对照组（19±4）ng／L、（3．9±0．8）ng／L（P〈0．01）；外周血IFNγ／与正常对照组相比差异无统计学意义；DM组的IFNα（56±22）ng／L、IFNβ（11．3±2．3）ng／L水平明显高于PM组（26±8）ng／L、（6．2±3．5）．g／I．（P〈0．05）。血清IFNα和IFNβ水平在有皮疹的患者中明显升高（P〈0．05）；IFNα、IFNβ表达水平与红细胞沉降率（ESR）（r=0．442，r=0．562，均P〈0．01）、C反应蛋白（CRP）（r=0．348，r=0．432，均P〈0．01）水平呈明显正相关。12例患者经治疗后IFNct、IFNB水平明显下降，差异有统计学意义（P〈0．01）。PM／DM患者组肌肉的IFNα、IFNβ、STATl基因表达明显高于正常对照组，差异有统计学意义（P〈0．05）。IFNαR1与正常对照组无明显变化。结论PM／DM患者血清和肌肉组织中的IFNα，IFNβ表达明显升高，与PM／DM病情活动度、严重性有一定的关系，STATl可能参与了IFNα，IFNβ在肌肉损害的信号传导。

Objective To detect the expression levels of interferons IFNα, IFNβ and IFNγ in theperipheral blood and muscle of patients with idiopathic inflammatory myopathies （IIM） so as to analyze their relationships with organ manifestations. Methods The serum levels of IFNα, IFNβ, IFNγand anti-Jol antibody were measured with ELISA （enzyme-linked immunosorbent assay ）. And the method of SYBR green dye based real-time quantitative PCR （polymerase chain reaction） was used to compare the expression levels of IFNα, IFNβ, interferon α receptor 1 （ IFNαR1 ）, signal transducer and activator of transcription 1 （ STAT1 ） in the IIM patients and normal controls. Results The serum levels of IFNα （ 50.2 ±21. 0） ng/L and IFNα（ 10. 7 ±5.4）ng/L in IIM patients were significantly higher than those in normal controls（ 18.6 ± 3.6） ng/L, （3.9 ± 0. 8 ） ng/L （ P 〈0.01 ）. And the serum levels of IFNα （55. 7 ± 21.9） ng/L and IFNβ （ 11.3 ± 2. 3 ） ng/L in DM patients were significantly higher than those in PM patients （ 26. 1 ± 8.2 ） ng/L, （6. 2 ±3.5 ） ng/L （ P 〈 0. 05 ）. The serum levels of IFNα and IFNβ correlated with the presence of skin rash （ P 〈 0.05 ）. And their serum concentrations correlated positively with erythrocyte sedimentation rate （ r = 0. 442, P = 0. 000 ; r =0. 562, P = 0. 000） and C-reactive protein （ r = 0. 348, P = 0. 004 ; r = 0. 432, P = 0. 005）respectively. The serum levels of IFNα and IFNβ decreased significantly after treatment in 12 PM/ DM （polymyositis/dermatomyositis） patients （P 〈0.01 ）. The mRNA expression levels of IFNα, IFNβ,IFNαR1 and STATI in PM/DM patients were higher than those in normal controls（P 〈0.05 ）. Conclusion The expression levels of IFNα and IFNβ in PM/DM patients are significantly higher than those in normal controls. And the increments had correlations with disease activity and severity. STAT1 has been implicated in signal transduction of IFNα and IFNβ in the muscles of PM/DM patients.