UK Iatrogenic Creutzfeldt-Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches
UK Iatrogenic Creutzfeldt-Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches
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DOI：
10.1007/s00401-016-1638-x
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发表时间：
2017-04-01
影响因子：
12.7
通讯作者：
Head, Mark W.
中科院分区：
文献类型：
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作者：
Ritchie, Diane L.;Barria, Marcelo A.;Head, Mark W.
克雅氏病（Creutzfeldt-Jakob disease，CJD）是一种典型的人类朊病毒病，最常以散发和遗传形式发生，但它也是可传播的，可以通过医疗程序获得，导致医源性CJD（iCJD）。世界范围内发生的最大数量的iCJD病例是由受污染的尸体垂体衍生的人生长激素（hGH）及其用于治疗原发性和继发性生长激素缺乏症引起的。我们报告了一个全面的，基于组织和分子遗传学分析的最大系列的英国生长激素-iCJD的情况下，迄今为止，包括在体外动力学分子模型的基因型因素影响朊病毒传播。结果显示朊病毒株和宿主基因型的相互作用，在管理的分子，病理和时间特征的英国HGH-iCJD流行病，并提供深入了解的适应机制时，朊病毒跨越基因型障碍。我们的结论是，所有可用的证据是一致的假设，英国hGH-iCJD流行导致的V2人类朊病毒株，这是与第二个最常见的形式散发性CJD的传输。
Creutzfeldt-Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show the interplay of prion strain and host genotype in governing the molecular, pathological and temporal characteristics of the UK hGH-iCJD epidemic and provide insights into the adaptive mechanisms involved when prions cross genotypic barriers. We conclude that all of the available evidence is consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is associated with the second most common form of sporadic CJD.