Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases

Abstract The cerebrospinal fluid (CSF) real-time quaking-induced conversion assay (RT-QuIC) is an ultrasensitive prion amyloid seeding assay for diagnosis of sporadic Creutzfeldt–Jakob disease (CJD) but several prion strains remain unexplored or resistant to conversion with commonly used recombinant...

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Autores principales:	Tze How Mok, Akin Nihat, Connie Luk, Danielle Sequeira, Mark Batchelor, Simon Mead, John Collinge, Graham S. Jackson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df04884ac887422694fcb1d5a25cc4e0
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spelling	oai:doaj.org-article:df04884ac887422694fcb1d5a25cc4e02021-12-02T11:35:58ZBank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases10.1038/s41598-021-84527-92045-2322https://doaj.org/article/df04884ac887422694fcb1d5a25cc4e02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84527-9https://doaj.org/toc/2045-2322Abstract The cerebrospinal fluid (CSF) real-time quaking-induced conversion assay (RT-QuIC) is an ultrasensitive prion amyloid seeding assay for diagnosis of sporadic Creutzfeldt–Jakob disease (CJD) but several prion strains remain unexplored or resistant to conversion with commonly used recombinant prion protein (rPrP) substrates. Here, bank vole (BV) rPrP was used to study seeding by a wide range of archived post-mortem human CSF samples from cases of sporadic, acquired and various inherited prion diseases in high throughput 384-well format. BV rPrP substrate yielded positive reactions in 70/79 cases of sporadic CJD [Sensitivity 88.6% (95% CI 79.5–94.7%)], 1/2 variant CJD samples, and 9/20 samples from various inherited prion diseases; 5/57 non-prion disease control CSFs had positive reactions, yielding an overall specificity of 91.2% (95% CI 80.1–97.1%). Despite limitations of using post-mortem samples and our results’ discrepancy with other studies, we demonstrated for the first time that BV rPrP is susceptible to conversion by human CSF samples containing certain prion strains not previously responsive in conventional rPrPs, thus justifying further optimisation for wider diagnostic and prognostic use.Tze How MokAkin NihatConnie LukDanielle SequeiraMark BatchelorSimon MeadJohn CollingeGraham S. JacksonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tze How Mok Akin Nihat Connie Luk Danielle Sequeira Mark Batchelor Simon Mead John Collinge Graham S. Jackson Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
description	Abstract The cerebrospinal fluid (CSF) real-time quaking-induced conversion assay (RT-QuIC) is an ultrasensitive prion amyloid seeding assay for diagnosis of sporadic Creutzfeldt–Jakob disease (CJD) but several prion strains remain unexplored or resistant to conversion with commonly used recombinant prion protein (rPrP) substrates. Here, bank vole (BV) rPrP was used to study seeding by a wide range of archived post-mortem human CSF samples from cases of sporadic, acquired and various inherited prion diseases in high throughput 384-well format. BV rPrP substrate yielded positive reactions in 70/79 cases of sporadic CJD [Sensitivity 88.6% (95% CI 79.5–94.7%)], 1/2 variant CJD samples, and 9/20 samples from various inherited prion diseases; 5/57 non-prion disease control CSFs had positive reactions, yielding an overall specificity of 91.2% (95% CI 80.1–97.1%). Despite limitations of using post-mortem samples and our results’ discrepancy with other studies, we demonstrated for the first time that BV rPrP is susceptible to conversion by human CSF samples containing certain prion strains not previously responsive in conventional rPrPs, thus justifying further optimisation for wider diagnostic and prognostic use.
format	article
author	Tze How Mok Akin Nihat Connie Luk Danielle Sequeira Mark Batchelor Simon Mead John Collinge Graham S. Jackson
author_facet	Tze How Mok Akin Nihat Connie Luk Danielle Sequeira Mark Batchelor Simon Mead John Collinge Graham S. Jackson
author_sort	Tze How Mok
title	Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
title_short	Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
title_full	Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
title_fullStr	Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
title_full_unstemmed	Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
title_sort	bank vole prion protein extends the use of rt-quic assays to detect prions in a range of inherited prion diseases
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/df04884ac887422694fcb1d5a25cc4e0
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Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases

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