PrpTSE distribution in a primate model of variant, sporadic, and iatrogenic Creutzfeldt-Jakob disease
PrpTSE distribution in a primate model of variant, sporadic, and iatrogenic Creutzfeldt-Jakob disease
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DOI：
10.1128/jvi.79.22.14339-14345.2005
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Lasmézas, CI
中科院分区：
文献类型：
--
作者：
Herzog, C;Rivière, J;Lasmézas, CI
人类朊病毒疾病，如克雅氏病（CJD），是神经退行性和致命的。散发克雅氏病（sCJD）可通过涉及中枢神经系统等高度感染器官的医疗程序在人与人之间传播。然而，由于人类感染了牛海绵状脑病（BSE）病原体，在变异型CjD （vCJD）中，淋巴网状组织也含有传染性海绵状脑病相关朊蛋白（Prp(TSE)），这对病源性传播具有特别严重的风险。已有两例与输血有关的病例记录在案。此外，最近对sCJD患者脾脏和肌肉中PrpTSE的观察提出了外周PrpTSE并不局限于vCJD病例的可能性。我们的目的是通过使用模仿人类疾病的非人灵长类动物模型来阐明人类tse的外周发病机制。采用高灵敏度的酶联免疫吸附法检测神经外Prp（TSE）。我们发现受影响的器官可以分为两组。首先是外周器官积聚大量的Prp(TSE)，这代表着医源性传播的高风险。此类别仅包括vCJD/BSE模型中的淋巴网状器官。第二种是与神经结构相关的含有少量PrPTSE的器官。这些是散发性、医源性和变异型CJD的肌肉、肾上腺和肠神经系统。与第一组器官相比，这种低水平的组织污染不受应变限制，似乎与毒剂通过神经的二次离心扩散有关。它可能代表了一种医源性传播的风险，尽管以前有报道称从人类外周器官到非人灵长类动物的传播率很低，但以前这一风险被低估了（5,10）。本研究为人体器官不同风险类别的划分以及对现有风险管理措施的合理重新评价提供了额外的实验依据。
Human prion diseases, such as Creutzfeldt-jakob disease (CJD), are neurodegenerative and fatal. Sporadic CjD (sCJD) can be transmitted between humans through medical procedures involving highly infected organs, such as the central nervous system. However, in variant CjD (vCJD), which is due to human contamination with the bovine spongiform encephalopathy (BSE) agent, lymphoreticular tissue also harbors the transmissible spongiform encephalopathy-associated prion protein (Prp(TSE)), which poses a particularly acute risk for iatrogenic transmission. Two blood transfusion-related cases are already documented. In addition, the recent observation of PrpTSE in spleen and muscle in sCJD raised the possibility that peripheral PrPTSE is not limited to vCJD cases. We aimed to clarify the peripheral pathogenesis of human TSEs by using a nonhuman primate model which mimics human diseases. A highly sensitive enzyme-linked immunosorbent assay was adapted to the detection of extraneural Prp(TSE). We show that affected organs can be divided into two groups. The first is peripheral organs accumulating large amounts of Prp(TSE), which represent a high risk of iatrogenic transmission. This category comprises only lymphoreticular organs in the vCJD/BSE model. The second is organs with small amounts of PrPTSE associated with nervous structures. These are the muscles, adrenal glands, and enteric nervous system in the sporadic, iatrogenic, and variant CJD models. In contrast to the first set of organs, this low level of tissue contamination is not strain restricted and seems to be linked to secondary centrifugal spread of the agent through nerves. It might represent a risk for iatrogenic transmission, formerly underestimated despite previous reports of low rates of transmission from peripheral organs of humans to nonhuman primates (5, 10). This study provides an additional experimental basis for the classification of human organs into different risk categories and a rational re-evaluation of current risk management measures.