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High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions
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High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions
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Journal Article
High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions
2017
Overview
An early and accurate
in vivo
diagnosis of rapidly progressive dementia remains challenging, despite its critical importance for the outcome of treatable forms, and the formulation of prognosis. Real-Time Quaking-Induced Conversion (RT-QuIC) is an
in vitro
assay that, for the first time, specifically discriminates patients with prion disease. Here, using cerebrospinal fluid (CSF) samples from 239 patients with definite or probable prion disease and 100 patients with a definite alternative diagnosis, we compared the performance of the first (PQ-CSF) and second generation (IQ-CSF) RT-QuIC assays, and investigated the diagnostic value of IQ-CSF across the broad spectrum of human prions. Our results confirm the high sensitivity of IQ-CSF for detecting human prions with a sub-optimal sensitivity for the sporadic CJD subtypes MM2C and MM2T, and a low sensitivity limited to variant CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. While we found no difference in specificity between PQ-CSF and IQ-CSF, the latter showed a significant improvement in sensitivity, allowing prion detection in about 80% of PQ-CSF negative CJD samples. Our results strongly support the implementation of IQ-CSF in clinical practice. By rapidly confirming or excluding CJD with high accuracy the assay is expected to improve the outcome for patients and their enrollment in therapeutic trials.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
14-3-3 Proteins - cerebrospinal fluid
/ 82/47
/ 82/80
/ Bovine spongiform encephalopathy
/ Creutzfeldt-Jakob Syndrome - cerebrospinal fluid
/ Creutzfeldt-Jakob Syndrome - diagnosis
/ Creutzfeldt-Jakob Syndrome - genetics
/ Humanities and Social Sciences
/ Humans
/ Prions
/ Prions - cerebrospinal fluid
/ PrPSc Proteins - cerebrospinal fluid
/ Science
