MxA induction may predict sustained virologic responses of chronic hepatitis B patients with IFN-α treatment
MxA induction may predict sustained virologic responses of chronic hepatitis B patients with IFN-α treatment
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DOI：
10.1089/jir.2006.0163
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发表时间：
2007-09-01
影响因子：
2.3
通讯作者：
Lu, Zhi-Meng
中科院分区：
文献类型：
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作者：
Kong, Xiao-Fei;Zhang, Xin-Xin;Lu, Zhi-Meng
本研究的目的是寻找潜在的生物标志物，以预测慢性乙型肝炎（CHB）患者对干扰素- α (ifn - α)治疗的持续病毒学反应。101例CHB患者接受聚乙二醇化IFN- α 2a治疗48周，随访24周，包括34例IFN应答者（IFN- rs）和67例IFN无应答者（IFN- nr）。体外用不同浓度的ifn - α处理外周血单个核细胞（PBMCs）和eb病毒转移B （EBV-B）细胞株后，用EMSA法检测激活的ifn刺激基因因子3 （ISGF3）和ifn - γ激活因子（GAF），用实时荧光定量PCR法检测MxA、OAS1和PKR mRNA。对MxA启动子的多态性进行基因分型以发现可能的关联。ifn - α激活的ISGF3和GAF水平在ifn - nr和IFN-Rs之间相似。然而，IFN- rs对MxA mRNA的诱导高于IFN- nrs，且高浓度IFN刺激时这种差异增加。OAS1和PKR mRNA的诱导在IFN-Rs和ifn - nr之间具有相似的模式。此外，MxA- 88g /T基因型的频率在IFN-Rs和ifn - nr之间存在显著差异，这种多态性也是功能性的，因为GG基因型患者的MxA mRNA诱导低于GT基因型患者。回归分析显示，10000 IU/mL IFN刺激后MxA mRNA诱导可以作为预测IFN- α的独立因素，曲线下面积（AUC）为0.838，IFN- rs阳性预测值为68%，IFN- rs阴性预测值为89%。ifn - α诱导的MxA mRNA可能预测慢性乙型肝炎患者对ifn - α治疗的持续病毒学反应。
The objective of this study was to find potential biomarkers for predicting sustained virologic responses to interferon-alpha ( IFN-alpha) treatment in chronic hepatitis B ( CHB) patients. A total of 101 CHB patients were treated with pegylated IFN-alpha 2a for 48 weeks and followed up for 24 weeks, including 34 IFN responders ( IFN-Rs) and 67 IFN nonresponders ( IFN-NRs). After peripheral blood mononuclear cells ( PBMCs) and Epstein-Barr virus-transferred B ( EBV-B) cell lines were treated with different concentrations of IFN-alpha in vitro, activated IFN-stimulated gene factor3 ( ISGF3) and IFN-gamma-activation factor ( GAF) were measured by EMSA, and MxA, OAS1, and PKR mRNA were measured by real-time PCR. Polymorphisms in the MxA promoter were genotyped to find the possible association. IFN-alpha-activated ISGF3 and GAF levels were similar between IFN-NRs and IFN-Rs. However, MxA mRNA induction in IFN-Rs was higher than that in IFN-NRs, and such discrepancy increased when highly concentrated IFN was used to stimulate. The OAS1 and PKR mRNA induction have a similar pattern between IFN-Rs and IFN-NRs. In addition, frequency of the MxA-88G/T genotype was significantly different between IFN-Rs and IFN-NRs, and this polymorphism was also functional because MxA mRNA induction in patients with GG genotype was lower than those with GT genotype. Regression analysis showed that MxA mRNA induction after 10,000 IU/mL IFN stimulation could serve as an independent factor for predicting IFN-alpha, with an area under curve ( AUC) of 0.838, a positive predictive value of 68% for IFN-Rs, and a negative predictive value of 89% for IFN-NRs. MxA mRNA induced by IFN-alpha might predict sustained virologic responses to IFN-alpha treatment in CHB patients.