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[诊断资讯] 新的血液检测可以测到朊病毒

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发表于 2016-12-30 11:00:05 | 显示全部楼层 |阅读模式

两项12月21日发表在Science Translational Medicine上的研究显示一个新的血液测试可以检测甚至很微量的朊病毒感染。

无可救药的朊病毒疾病——如牛的疯牛病(BSE)和人的变异型克雅氏病(vCJD),通过将一个正常的称为PRP的脑蛋白扭曲到致病“朊病毒”的形状,造成杀死大脑中神经细胞的结果。在英国,多达30000人可能是朊病毒的携带者,可能是使用疯牛病感染的牛肉而获得的。卫生官员担心,受感染的人可以无意中通过输血将朊病毒传给别人。有四个这样的案件已经被记录。但到目前为止,还没有办法为感染蛋白筛查血液样本。

在文章描述的测试中描述了该研究的设计是用纤维蛋白溶酶原蛋白包被磁性纳米珠。纤维蛋白溶酶原蛋白是结合朊病毒蛋白的。清洗珠子可以除去血液中的其他物质。研究人员然后将正常的PrP加到磁珠中去。如果任何朊病毒和磁珠结合、传染性蛋白会将PrP扭曲成朊病毒的形式,也会和磁珠结合。经过多轮结合,研究人员可以扩增足够的检测信号来测试哪个样本有vCJD朊病毒。

在这两项研究中,没有健康的人或其他退化性脑疾病(包括阿尔茨海默氏症和帕金森氏症)的人有血液中存在感染性蛋白的证据。83人中只有一个有不定期发生的克雅氏病形式的人测试呈阳性。在两篇文章中,研究人员都是收集冰冻的血液样本,31个月和16个月查出vCJD症状朊病毒。这些结果表明,试验特定针对vCJD朊病毒形式。

来源:生物探索

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 楼主| 发表于 2016-12-30 11:00:42 | 显示全部楼层
Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease

Daisy Bougard1,*, Jean-Philippe Brandel2,3,4, Maxime Bélondrade1, Vincent Béringue5, Christiane Segarra1, Hervé Fleury6, Jean-Louis Laplanche4,7, Charly Mayran1, Simon Nicot1, Alison Green8, Arlette Welaratne3, David Narbey9, Chantal Fournier-Wirth1, Richard Knight8, Robert Will8, Pierre Tiberghien9,10, Stéphane Haïk2,3,4 and Joliette Coste

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.

http://stm.sciencemag.org/content/8/370/370ra182

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 楼主| 发表于 2016-12-30 11:01:17 | 显示全部楼层
Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease

Luis Concha-Marambio1,2, Sandra Pritzkow1, Fabio Moda1,3, Fabrizio Tagliavini3, James W. Ironside4, Paul E. Schulz1 and Claudio Soto

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrPSc) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrPSc could be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrPSc concentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology.

http://stm.sciencemag.org/content/8/370/370ra183
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