Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.
Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.
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脑脊液中人类prion检测的诊断和预后价值。
DOI：
10.1002/ana.24833
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发表时间：
2017-01
影响因子：
11.2
通讯作者：
Safar JG
中科院分区：
文献类型：
--
作者：
Foutz A;Appleby BS;Hamlin C;Liu X;Yang S;Cohen Y;Chen W;Blevins J;Fausett C;Wang H;Gambetti P;Zhang S;Hughson A;Tatsuoka C;Schonberger LB;Cohen ML;Caughey B;Safar JG
已经提出了几种朊病毒扩增系统用于检测脑脊液（CSF）中的朊病毒，最近，用第二代实时震动诱导转换（RT-QuIC）测量朊病毒接种活性。本研究的目的是研究RT-QuIC朊病毒检测在朊病毒疾病的广泛表型谱中的诊断性能。我们对2,141例患有快速进展性神经系统疾病的患者进行了CSF RT-QuIC检测，确定了272例尸检病例的诊断灵敏度和特异性，并评估了PRNP基因突变和多态性以及1型或2型人类朊病毒对诊断性能的影响。在盲法回顾性分析中，CSF RT-QuIC的98.5%诊断特异性和92%灵敏度与盲法前瞻性研究的100%特异性和95%灵敏度相匹配。CSF RT-QuIC将94%的散发性克雅氏病（sCJD）MM 1与sCJD MM 2表型区分开来，将80%的sCJD VV 2与sCJD VV 1区分开来。混合朊病毒1-2型和密码子129杂合子病例产生中间CSF RT-QuIC模式，而遗传性朊病毒疾病显示每个PRNP基因突变的不同特征。改进的CSF RT-QuIC的诊断性能上级于朊病毒疾病的替代标志物测试，例如14-3-3和Tau蛋白，并且与PRNP基因测序一起，该测试允许在体内区分主要的朊病毒亚型。这种分化有助于预测临床病理表型和疾病的持续时间-这是设想的治疗干预的两个重要考虑因素。
Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases which were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and Type 1 or Type 2 of human prions on diagnostic performance. The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1–2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, while genetic prion diseases revealed distinct profiles for each PRNP gene mutation. The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and Tau proteins and together with PRNP gene sequencing, the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease—two important considerations for envisioned therapeutic interventions.