Identification of host genes responsible for the treatment response of interferon therapy for the patients with chronic hepatitis C

本研究证实干扰素刺激基因(ISGs)的诱导与干扰素治疗的疗效密切相关。治疗前肝脏中ISGs的表达上调可能会影响肝脏对ISGs的从头诱导作用。有趣的是，治疗前肝脏中ISGs的上调与IL28的微小基因型密切相关。因此，IL28B基因可能参与了肝脏不同类型ISGs的诱导。IL28B主要基因型患者的肝脏ISGs表达与PBMC的ISGs表达显著相关，而IL28B次要基因型患者的肝脏ISGs表达与PBMC的ISGs表达无明显相关性。用激光捕获显微解剖对肝活检标本进行详细检查，发现IL28B微小基因携带者肝小叶内免疫细胞的浸润受损。IL28B亚型的这些免疫调节失衡可能是干扰素治疗反应差的原因之一

This study demonstrated that the induction of interferon stimulated genes(ISGs) was closely related to the treatment response to IFN therapy. Up-regulated ISGs expression of in liver before treatment might impair the de novo ISGs induction in liver. Interestingly, up-regulated ISGs in liver before treatment were closely related to IL28 minor genotype. Therefore, Il28B genotype must be involved in different ISGs induction in liver. There was a significant correlation of ISGs expression between the liver and PBMC in patients with IL28B major genotype, while no correlation was found in patients with IL28B minor genotype. Detailed examination of liver biopsy specimen by laser capture micro dissection revealed the impaired infiltration of immune cells in liver lobules in patients with IL28B minor genotype. These immune regulatory imbalances of IL28B minor genotype might contribute to the poor response to IFN therapy