Giannelli Gianluigi, Guadagnino Graziana, Dentico Pietro, Antonelli Guido, Antonaci Salvatore
Department of Internal Medicine, Immunology and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy.
J Interferon Cytokine Res. 2004 Nov;24(11):659-63. doi: 10.1089/jir.2004.24.659.
The effectiveness of therapy for chronic hepatitis C (CHC) patients has greatly improved in the last few years, and the gold standard is currently held to be pegylated interferon (IFN) in combination with ribavirin. Overall, however, the percentage of patients achieving a sustained virologic response (SVR) is only around 50%,and it is not possible to predict those patients who will benefit from therapy. The molecular mechanisms underlying lack of therapeutic response remain unknown. In this study, we investigated the tissue expression of MxA and RNA-dependent protein kinase (PKR), two antiviral proteins modulated by IFN, in biopsy samples from hepatitis C patients before the beginning of therapy. Our results show that expression of MxA, but not of PKR, is significantly lower in responders compared with nonresponders. No differences were observed regarding the hepatitis C virus (HCV) genotype and the viral load. These results suggest that expression of the MxA protein could play a role among the mechanisms underlying responsiveness to therapy.
在过去几年中,慢性丙型肝炎(CHC)患者的治疗效果有了很大改善,目前的金标准是聚乙二醇化干扰素(IFN)联合利巴韦林。然而,总体而言,实现持续病毒学应答(SVR)的患者比例仅约为50%,并且无法预测哪些患者将从治疗中获益。治疗无反应背后的分子机制仍然未知。在本研究中,我们调查了丙型肝炎患者治疗开始前活检样本中Mx A和RNA依赖性蛋白激酶(PKR)这两种受IFN调节的抗病毒蛋白的组织表达。我们的结果表明,与无反应者相比,有反应者中Mx A的表达显著降低,而PKR的表达则无显著差异。在丙型肝炎病毒(HCV)基因型和病毒载量方面未观察到差异。这些结果表明,Mx A蛋白的表达可能在治疗反应的潜在机制中起作用。