Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease
Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease
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DOI：
10.1056/nejmoa030351
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发表时间：
2003-11-06
影响因子：
158.5
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Glatzel, M;Abela, E;Aguzzi, A
背景：在散发性克雅氏病患者中，病理性疾病相关朊蛋白（PrP（sup Sc））仅在中枢神经系统和嗅神经组织中发现。了解PrP（sup Sc）在Creutzfeldt-Jakob病中的分布对于分类和诊断，甚至可能对于Prevent.METHODS：我们使用了一种高度敏感的检测方法--涉及PrP（sup Sc）的浓度，通过磷钨酸钠的差异沉淀，将Western印迹分析的灵敏度提高了三个数量级--在1996年至2002年期间死亡的36例散发性Creutzfeldt-Jakob病患者的神经器官中寻找PrP（sup Sc）。此外，我们发现PrP（supSc）在10的28个脾标本和8的32个尿道肌肉样本。3例患者在脾脏和肌肉标本中均检测到PrP（sup Sc）。与神经性朊蛋白（supSc）的患者有一个显着较长的病程，更有可能有罕见的分子变异的散发性Creutzfeldt-Jakob病比没有神经性朊蛋白（supSc）的患者。结论：使用敏感的技术，我们确定了神经性沉积的朊蛋白（supSc）的脾脏和肌肉样本中约三分之一的患者死于散发性Creutzfeldt-Jakob病。神经外PrP（sup Sc）似乎与疾病持续时间较长相关。
BACKGROUND:In patients with sporadic Creutzfeldt-Jakob disease, pathologic disease-associated prion protein (PrP(sup Sc)) has been identified only in the central nervous system and olfactory-nerve tissue. Understanding the distribution of PrP(sup Sc) in Creutzfeldt-Jakob disease is important for classification and diagnosis and perhaps even for prevention.METHODS:We used a highly sensitive method of detection -- involving the concentration of PrP(sup Sc) by differential precipitation with sodium phosphotungstic acid, which increased the sensitivity of Western blot analysis by up to three orders of magnitude -- to search for PrP(sup Sc) in extraneural organs of 36 patients with sporadic Creutzfeldt-Jakob disease who died between 1996 and 2002.RESULTS:PrP(sup Sc) was present in the brain tissue of all patients. In addition, we found PrP(sup Sc) in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrP(sup Sc) in both spleen and muscle specimens. Patients with extraneural PrP(sup Sc) had a significantly longer duration of disease and were more likely to have uncommon molecular variants of sporadic Creutzfeldt-Jakob disease than were patients without extraneural PrP(sup Sc).CONCLUSIONS:Using sensitive techniques, we identified extraneural deposition of PrP(sup Sc) in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt-Jakob disease. Extraneural PrP(sup Sc) appears to correlate with a long duration of disease.