Variant Creutzfeldt-Jakob disease (vCJD) is a devastating disease caused by transmission of bovine spongiform encephalopathy to humans. Although vCJD cases are now rare, evidence from appendix surveys suggests that a small proportion of the United Kingdom population may be infected without showing signs of disease. These “silent” carriers could present a risk of iatrogenic vCJD transmission through medical procedures or blood/organ donation, and currently there are no validated tests to identify infected asymptomatic individuals using easily accessible samples. To address this issue, we evaluated the performance of 3 blood-based assays in a blinded study, using longitudinal sample series from a well-established large animal model of vCJD. The assays rely on amplification of misfolded prion protein (PrPSc; a marker of prion infection) and include real-time quaking-induced conversion (RT-QuIC), and 2 versions of protein misfolding cyclic amplification (PMCA). Although diagnostic sensitivity was higher for both PMCA assays (100%) than RT-QuIC (61%), all 3 assays detected prion infection in blood samples collected 26 months before the onset of clinical signs and gave no false-positive results. Parallel estimation of blood prion infectivity titers in a sensitive transgenic mouse line showed positive correlation of infectivity with PrPSc detection by the assays, suggesting that they are suitable for detection of asymptomatic vCJD infection in the human population. This study represents, to our knowledge, the largest comparison to date of preclinical prion detection in blood samples from a relevant animal model. The outcomes will guide efforts to improve early detection of prion disease and reduce infection risks in humans.

中文翻译：

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使用 3 种检测方法对临床前绵羊血液样本中朊病毒感染的纵向检测进行比较


变异型克雅氏病 （vCJD） 是一种由牛海绵状脑病传播给人类引起的毁灭性疾病。尽管 vCJD 病例现在很少见，但附录调查的证据表明，英国人口的一小部分可能被感染而没有表现出疾病迹象。这些“沉默”携带者可能存在通过医疗程序或血液/器官捐献传播医源性 vCJD 的风险，目前还没有经过验证的测试来使用易于获取的样本来识别感染的无症状个体。为了解决这个问题，我们在一项盲法研究中评估了 3 种基于血液的测定的性能，使用来自成熟的 vCJD 大型动物模型的纵向样本系列。这些检测依赖于错误折叠朊病毒蛋白 （PrPSc;朊病毒感染的标志物） 的扩增，包括实时震动诱导转化 （RT-QuIC） 和 2 种版本的蛋白质错误折叠循环扩增 （PMCA）。尽管两种 PMCA 检测的诊断敏感性 （100%） 都高于 RT-QuIC （61%），但所有 3 种检测均在临床症状出现前 26 个月采集的血液样本中检测到朊病毒感染，并且没有给出假阳性结果。敏感转基因小鼠品系中血朊病毒感染性滴度的平行估计显示感染性与测定法检测的 PrPSc 呈正相关，表明它们适用于检测人类人群中的无症状 vCJD 感染。据我们所知，这项研究代表了迄今为止在相关动物模型血液样本中进行临床前朊病毒检测的最大比较。这些结果将指导改善朊病毒病的早期检测和降低人类感染风险的努力。