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Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes
Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible, rapidly progressive and fatal neurodegenerative disease. The transmissible agent linked to sCJD is composed of the misfolded form of the host-encoded prion protein. The combination of histopathological and biochemical analyses has allowed...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6576779/ https://www.ncbi.nlm.nih.gov/pubmed/31206560 http://dx.doi.org/10.1371/journal.pone.0218509 |
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author | Piconi, Gabriele Peden, Alexander H. Barria, Marcelo A. Green, Alison J. E. |
author_facet | Piconi, Gabriele Peden, Alexander H. Barria, Marcelo A. Green, Alison J. E. |
author_sort | Piconi, Gabriele |
collection | PubMed |
description | Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible, rapidly progressive and fatal neurodegenerative disease. The transmissible agent linked to sCJD is composed of the misfolded form of the host-encoded prion protein. The combination of histopathological and biochemical analyses has allowed the identification and sub-classification of six sCJD subtypes. This classification depends on the polymorphic variability of codon 129 of the prion protein gene and the PrP(res) isotype, and appears to be associated with neuropathological and clinical features. Currently, sCJD subtyping is only fully achievable post mortem. However, a rapid and non-invasive method for discriminating sCJD subtypes in vita would be invaluable for the clinical management of affected individuals, and for the selection of participants for clinical trials. The CSF analysis by Real Time Quaking Induced Conversion (RT-QuIC) reaction is the most sensitive and specific ante mortem sCJD diagnostic test available to date, and it is used by a number of laboratories internationally. RT-QuIC takes advantage of the natural replication mechanisms of prions by template-induced misfolding, employing recombinant prion protein as reaction substrate. We asked whether epitope mapping, of the RT-QuIC reaction products obtained from seeding RT-QuIC with brain and CSF samples from each of the six molecular subtypes of sCJD could be employed to distinguish them and therefore achieve in vita sCJD molecular subtyping. We found that it is possible to distinguish the RT-QuIC products generated by sCJD biological samples from the ones generated by spontaneous conversion in the negative controls, but that different sCJD subtypes generate very similar, if not identical RT-QuIC reaction products. We concluded that whilst RT-QuIC has demonstrable diagnostic value it has limited prognostic value at this point in time. |
format | Online Article Text |
id | pubmed-6576779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65767792019-06-28 Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes Piconi, Gabriele Peden, Alexander H. Barria, Marcelo A. Green, Alison J. E. PLoS One Research Article Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible, rapidly progressive and fatal neurodegenerative disease. The transmissible agent linked to sCJD is composed of the misfolded form of the host-encoded prion protein. The combination of histopathological and biochemical analyses has allowed the identification and sub-classification of six sCJD subtypes. This classification depends on the polymorphic variability of codon 129 of the prion protein gene and the PrP(res) isotype, and appears to be associated with neuropathological and clinical features. Currently, sCJD subtyping is only fully achievable post mortem. However, a rapid and non-invasive method for discriminating sCJD subtypes in vita would be invaluable for the clinical management of affected individuals, and for the selection of participants for clinical trials. The CSF analysis by Real Time Quaking Induced Conversion (RT-QuIC) reaction is the most sensitive and specific ante mortem sCJD diagnostic test available to date, and it is used by a number of laboratories internationally. RT-QuIC takes advantage of the natural replication mechanisms of prions by template-induced misfolding, employing recombinant prion protein as reaction substrate. We asked whether epitope mapping, of the RT-QuIC reaction products obtained from seeding RT-QuIC with brain and CSF samples from each of the six molecular subtypes of sCJD could be employed to distinguish them and therefore achieve in vita sCJD molecular subtyping. We found that it is possible to distinguish the RT-QuIC products generated by sCJD biological samples from the ones generated by spontaneous conversion in the negative controls, but that different sCJD subtypes generate very similar, if not identical RT-QuIC reaction products. We concluded that whilst RT-QuIC has demonstrable diagnostic value it has limited prognostic value at this point in time. Public Library of Science 2019-06-17 /pmc/articles/PMC6576779/ /pubmed/31206560 http://dx.doi.org/10.1371/journal.pone.0218509 Text en © 2019 Piconi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Piconi, Gabriele Peden, Alexander H. Barria, Marcelo A. Green, Alison J. E. Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes |
title | Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes |
title_full | Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes |
title_fullStr | Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes |
title_full_unstemmed | Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes |
title_short | Epitope mapping of the protease resistant products of RT-QuIC does not allow the discrimination of sCJD subtypes |
title_sort | epitope mapping of the protease resistant products of rt-quic does not allow the discrimination of scjd subtypes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6576779/ https://www.ncbi.nlm.nih.gov/pubmed/31206560 http://dx.doi.org/10.1371/journal.pone.0218509 |
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