Interferon lambdas: the next cytokine storm.
Interferon lambdas: the next cytokine storm.
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DOI：
10.1136/gut.2010.222976
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发表时间：
2011-09
期刊：
影响因子：
24.5
通讯作者：
Barnes E
中科院分区：
文献类型：
--
作者：
Kelly C;Klenerman P;Barnes E
二十年来，科学界一直试图了解为什么有些人能够清除丙型肝炎病毒 (HCV)，而另一些人则不能。最近，几项大型全基因组关联研究发现了与干扰素 lambda 3 (IFNλ3) 相关的单核苷酸多态性 (SNP)，这些单核苷酸多态性与 HCV 感染的自发消退和成功治疗相关。这些观察结果正在引发激烈的研究活动；希望 IFNλ3 基因变异可以作为治疗结果的重要预测生物标志物，并为病毒控制所涉及的生物途径提供新的见解。现在可以设想 HCV 的药物基因组治疗方法，将宿主遗传变异与其他因素结合到预测治疗算法中。与HCV感染临床结果相关的SNP与IFNλ3基因本身有一定距离，并且因果遗传变异尚未明确定义。找到这些致病变异、详细绘制 IFNλ3 信号通路图谱并确定如此诱导的下游遗传特征，将阐明 IFNλ3 在 HCV 发病机制中的作用。目前正在进行评估外源性 IFNλ3 治疗 HCV 安全性和有效性的临床研究。早期结果表明，IFNλ3 治疗可抑制 HCV 复制，且副作用有限。然而，健康志愿者和 HCV 感染患者的肝毒性已有报道。本综述讨论了将 IFNλ3 与 HCV 自发消退和治疗诱导清除联系起来的遗传学研究及其在临床实践中的潜在影响、目前了解的 IFNλ3 生物学及其对 HCV 感染的影响，并描述了评估该细胞因子在 HCV 患者治疗中作用的早期研究。
For two decades the scientific community has sought to understand why some people clear hepatitis C virus (HCV) and others do not. Recently, several large genome-wide association studies have identified single nucleotide polymorphisms (SNPs) linked to interferon lambda 3 (IFNλ3) that are associated with the spontaneous resolution and successful treatment of HCV infection. These observations are generating intense research activity; the hope is that IFNλ3 genetic variants may serve as important predictive biomarkers of treatment outcome and offer new insights into the biological pathways involved in viral control. A pharmacogenomic treatment approach for HCV can now be envisaged, with the incorporation of host genetic variants into a predictive treatment algorithm with other factors. The SNPs associated with the clinical outcome of HCV infection are located some distance from the IFNλ3 gene itself, and causal genetic variants have yet to be clearly defined. Locating these causal variants, mapping in detail the IFNλ3 signalling pathways and determining the downstream genetic signature so induced will clarify the role of IFNλ3 in the pathogenesis of HCV. Clinical studies assessing safety and efficacy in the treatment of HCV with exogenous IFNλ3 are currently underway. Early results suggest that IFNλ3 treatment inhibits HCV replication and is associated with a limited side effect profile. However, hepatotoxicity in both healthy volunteers and HCV-infected patients has been described. This review discusses the genetic studies that link IFNλ3 to both the spontaneous resolution and treatment-induced clearance of HCV and the potential impact of this in clinical practice, the biology of IFNλ3 as currently understood and how this may impact on HCV infection, and describes the early studies that assess the role of this cytokine in the treatment of patients with HCV.
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影响因子：
29.4
作者：
McCarthy JJ;Li JH;Thompson A;Suchindran S;Lao XQ;Patel K;Tillmann HL;Muir AJ;McHutchison JG
通讯作者：
McHutchison JG
影响因子：
20.3
作者：
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通讯作者：
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影响因子：
13.5
作者：
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通讯作者：
Francisca Gonzalez-Escribano, Maria
影响因子：
158.5
作者：
Kenny-Walsh, E
通讯作者：
Kenny-Walsh, E
影响因子：
12.4
作者：
Morrow, Matthew P.;Yan, Jian;Weiner, David B.
通讯作者：
Weiner, David B.