Hepatic expression of type I interferon receptor for predicting response to interferon therapy in chronic hepatitis C patients: a comparison of immunohistochemical method vs. competitive polymerase chain reaction assay
Hepatic expression of type I interferon receptor for predicting response to interferon therapy in chronic hepatitis C patients: a comparison of immunohistochemical method vs. competitive polymerase chain reaction assay
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DOI：
10.1016/s1386-6346(02)00312-1
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发表时间：
2003-04-01
影响因子：
4.2
通讯作者：
Okita, K
中科院分区：
文献类型：
--
作者：
Fujiwara, D;Hino, K;Okita, K
本研究的重点是确定肝脏中I型干扰素（IFN）受体亚单位IFN α受体（IFNAR 1）和IFN α/β受体（IFNAR 2）的mRNA和蛋白质表达水平，并评估哪种定量方法在预测慢性丙型肝炎患者对IFN的反应中最有用。随后用IFN治疗的41例慢性丙型肝炎患者的肝活检标本用IFNAR 1和IFNAR 2抗体进行免疫染色，并使用竞争性聚合酶链反应分析两种受体亚单位mRNA水平。IFNAR 1和IFNAR 2在所有肝标本的肝细胞的细胞膜和细胞质中观察到免疫染色。IFNAR 1（r = 0.45，P = 0.012）和IFNAR 2（r = 0.46，P = 0.009）mRNA在肝组织中的表达与其蛋白表达呈弱相关。IFNAR 1标记指数（136.7 +/- 94.1 vs. 77.4 +/- 76.8，P = 0.032）和IFNAR 2（153.1 +/- 80.2 vs. 87.2 +/- 75.5，持续病毒学应答者（n = 17）的肝脏标本中的总RNA水平（P = 0.011）显著高于非持续病毒学应答者（n = 17）。24），而任一受体亚基的mRNA水平在反应组之间没有差异。这些结果表明，在预测慢性丙型肝炎患者对IFN的反应方面，肝脏I型IFN受体的蛋白表达比其mRNA表达更有用。(C)2002 Elsevier Science B. V.保留所有权利。
The focus of this study is to determine both mRNA and protein expression levels of the type I interferon (IFN) receptor subunits, IFNalpha receptor (IFNAR1) and IFNalpha/beta receptor (IFNAR2), in the liver, and to assess which quantification method is most useful in predicting response to IFN in chronic hepatitis C patients. Liver biopsy specimens from 41 chronic hepatitis C patients subsequently treated with IFN were immunostained with IFNAR1 and IFNAR2 antibodies, and also analyzed for both receptor subunit mRNA levels, using competitive polymerase chain reaction. Immunostaining of IFNAR1 and IFNAR2 was observed in the cell membrane and cytoplasm of hepatocytes in all liver specimens. Hepatic expression of IFNAR1 (r = 0.45, P = 0.012) or IFNAR2 mRNA (r = 0.46, P = 0.009) was weakly correlated with their protein expression in hepatocytes. The labeling indexes of IFNAR1 (136.7 +/- 94.1 vs. 77.4 +/- 76.8, P = 0.032) and IFNAR2 (153.1 +/- 80.2 vs. 87.2 +/- 75.5, P = 0.011) in liver specimens were significantly higher in sustained virologic responders (n = 17) than in non-sustained virologic responders (n = 24), while mRNA levels of either receptor subunit did not differ between response groups. These results suggest that protein expression-of the type I IFN receptor in liver is a more useful measure than its mRNA expression in predicting response to IFN in chronic hepatitis C patients. (C) 2002 Elsevier Science B.V. All rights reserved.