Rapid and simple detection of IFN-neutralizing antibodies in chronic hepatitis C non-responsive to IFN-α
Rapid and simple detection of IFN-neutralizing antibodies in chronic hepatitis C non-responsive to IFN-α
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DOI：
10.1002/jmv.20506
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发表时间：
2006-01-01
影响因子：
12.7
通讯作者：
Kochs, G
中科院分区：
文献类型：
--
作者：
Jorns, C;Holzinger, D;Kochs, G
对于慢性丙型肝炎和多发性硬化患者干扰素（IFN）治疗失败的不同机制已经提出，例如，IFN中和抗体的存在。在这项研究中，一种新的检测系统的基础上IFN-诱导Mx启动子用于检测慢性丙型肝炎患者血清中的IFN-中和抗体。为了监测IFN治疗患者的IFN生物活性，建立了PBMC中MxA基因表达的实时RT-PCR。使用这两种方法，慢性丙型肝炎病毒（HCV）感染的患者接受干扰素治疗和治疗诱导HCV清除的患者进行监测。重要的是，在38例慢性HCV感染患者的血清中检测到中和抗IFN抗体，这些患者对治疗没有反应，但在IFN治疗后清除HCV的患者血清中没有检测到中和抗IFN抗体。有趣的是，这些抗体的存在与开始IFN-α治疗后PBMC中MxA诱导的缺乏相关。对一名患者血清的回顾性分析显示，在四种不成功的IFN治疗中的第一种之后，抗IFN-chi抗体已经产生，这表明中和抗体可能导致先前IFN治疗的失败。总之，建立了一种新的筛选测定法，其可能有助于测试IFN无应答者是否存在临床相关的抗-IFN-chi抗体，并用于选择不被这些抗体中和的替代IFN制剂。
Different mechanisms have been proposed for the failure of interferon (IFN) therapy in patients with chronic hepatitis C and multiple sclerosis, for example, the presence of IFN-neutralizing antibodies. In this study, a novel assay system based on the IFN-inducible Mx-promoter was used to detect IFN-neutralizing antibodies in sera of patients with chronic hepatitis C. To monitor IFN bioactivity in IFN-treated patients, a real-time RT-PCR for MxA gene expression in PBMCs was established. Using these two methods, patients with chronic hepatitis C virus (HCV) infection receiving IFN therapy and patients with treatment induced HCV clearance were monitored. Importantly, neutralizing anti-IFN antibodies were detected in the sera of 3 of 38 chronically HCV-infected patients who failed to respond to therapy but none in sera of patients who cleared HCV after IFN therapy. Interestingly, the presence of these antibodies correlated with the lack of MxA induction in PBMCs after initiation of IFN-chi therapy. Retrospective analysis of one patient's sera, revealed that the anti-IFN-chi antibodies had already developed after the first of four unsuccessful IFN therapies, suggesting that neutralizing antibodies may have contributed to the failure of previous IFN treatments. In summary, a novel screening assay was established that may be helpful for testing IFN non-responders for the presence of clinically relevant anti-IFN-chi antibodies and for selecting alternative IFN preparations not neutralized by these antibodies.