Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease
Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease
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DOI：
10.1126/scitranslmed.aag1257
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发表时间：
2016-12-21
影响因子：
17.1
通讯作者：
Coste, Joliette
中科院分区：
文献类型：
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作者：
Bougard, Daisy;Brandel, Jean-Philippe;Coste, Joliette
变异型克雅氏病（vCJD）是一种人类朊病毒疾病，由食用被引起牛海绵状脑病的病原体污染的肉制品引起。有越来越多的证据支持存在可能通过输血传播疾病的沉默携带者群体。迫切需要开发一种针对有症状的vCJD患者和无症状携带者的血液筛查方法。我们发现，一种结合纤溶酶原头捕获和蛋白质错误折叠循环扩增（PMCA）技术的诊断分析，在所需的飞摩尔范围内，始终检测到法国和英国vCJD病例中微量的异常朊病毒蛋白。该方法从两个疫情最严重的国家的256份血浆样本中盲法鉴定出18名临床vCJD患者，灵敏度为100%[95%置信区间（CI）， 81.5 - 100%]，分析特异性为99.2% (95% CI, 95.9 - 100%)，诊断特异性为100% （95% CI, 96.5 - 100%）。该试验还允许在两名后来发展为vCJD的献血者的临床发病前1.3年和2.6年检测到朊病毒的沉默携带。这些数据为验证PMCA技术作为vCJD的血液诊断测试提供了关键的一步，并支持其检测症状前患者的潜力，这是限制vCJD通过输血传播风险的先决条件。
Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity [95% confidence interval (CI), 81.5 to 100%], 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion.