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Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD

OBJECTIVE: Real‐time quaking‐induced conversion (RT‐QuIC) assays detect prion‐seeding activity in a variety of human biospecimens, including cerebrospinal fluid and olfactory mucosa swabs. The assay has shown high diagnostic accuracy in patients with prion disorders. Recently, advances in these test...

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Autores principales: Orrú, Christina D., Groveman, Bradley R., Foutz, Aaron, Bongianni, Matilde, Cardone, Franco, McKenzie, Neil, Culeux, Audrey, Poleggi, Anna, Grznarova, Katarina, Perra, Daniela, Fiorini, Michele, Liu, Xiaoqin, Ladogana, Anna, Sbriccoli, Marco, Hughson, Andrew G., Haïk, Stéphane, Green, Alison J., Geschwind, Michael D., Pocchiari, Maurizio, Safar, Jiri G., Zanusso, Gianluigi, Caughey, Byron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664259/
https://www.ncbi.nlm.nih.gov/pubmed/33185334
http://dx.doi.org/10.1002/acn3.51219
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author Orrú, Christina D.
Groveman, Bradley R.
Foutz, Aaron
Bongianni, Matilde
Cardone, Franco
McKenzie, Neil
Culeux, Audrey
Poleggi, Anna
Grznarova, Katarina
Perra, Daniela
Fiorini, Michele
Liu, Xiaoqin
Ladogana, Anna
Sbriccoli, Marco
Hughson, Andrew G.
Haïk, Stéphane
Green, Alison J.
Geschwind, Michael D.
Pocchiari, Maurizio
Safar, Jiri G.
Zanusso, Gianluigi
Caughey, Byron
author_facet Orrú, Christina D.
Groveman, Bradley R.
Foutz, Aaron
Bongianni, Matilde
Cardone, Franco
McKenzie, Neil
Culeux, Audrey
Poleggi, Anna
Grznarova, Katarina
Perra, Daniela
Fiorini, Michele
Liu, Xiaoqin
Ladogana, Anna
Sbriccoli, Marco
Hughson, Andrew G.
Haïk, Stéphane
Green, Alison J.
Geschwind, Michael D.
Pocchiari, Maurizio
Safar, Jiri G.
Zanusso, Gianluigi
Caughey, Byron
author_sort Orrú, Christina D.
collection PubMed
description OBJECTIVE: Real‐time quaking‐induced conversion (RT‐QuIC) assays detect prion‐seeding activity in a variety of human biospecimens, including cerebrospinal fluid and olfactory mucosa swabs. The assay has shown high diagnostic accuracy in patients with prion disorders. Recently, advances in these tests have led to markedly improved diagnostic sensitivity and reduced assay times. Accordingly, an algorithm has been proposed that entails the use of RT‐QuIC analysis of both sample types to diagnose sporadic Creutzfeldt‐Jakob disease with nearly 100% accuracy. Here we present a multi‐center evaluation (ring trial) of the reproducibility of these improved “second generation” RT‐QuIC assays as applied to these diagnostic specimens. METHODS: Cerebrospinal fluid samples were analyzed from subjects with sporadic Creutzfeldt‐Jakob (n = 55) or other neurological diseases (n = 45) at multiple clinical centers. Olfactory mucosa brushings collected by multiple otolaryngologists were obtained from nine sporadic Creutzfeldt‐Jakob disease cases and 19 controls. These sample sets were initially tested blindly by RT‐QuIC by a coordinating laboratory, recoded, and then sent to five additional testing laboratories for blinded ring trial testing. RESULTS: Unblinding of the results by a third party indicated 98‐100% concordance between the results obtained by the testing of these cerebrospinal fluid and nasal brushings at the six laboratories. INTERPRETATION: This second‐generation RT‐QuIC assay is highly transferrable, reproducible, and therefore robust for the diagnosis of sporadic Creutzfeldt‐Jakob disease in clinical practice.
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spelling pubmed-76642592020-11-17 Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD Orrú, Christina D. Groveman, Bradley R. Foutz, Aaron Bongianni, Matilde Cardone, Franco McKenzie, Neil Culeux, Audrey Poleggi, Anna Grznarova, Katarina Perra, Daniela Fiorini, Michele Liu, Xiaoqin Ladogana, Anna Sbriccoli, Marco Hughson, Andrew G. Haïk, Stéphane Green, Alison J. Geschwind, Michael D. Pocchiari, Maurizio Safar, Jiri G. Zanusso, Gianluigi Caughey, Byron Ann Clin Transl Neurol Research Articles OBJECTIVE: Real‐time quaking‐induced conversion (RT‐QuIC) assays detect prion‐seeding activity in a variety of human biospecimens, including cerebrospinal fluid and olfactory mucosa swabs. The assay has shown high diagnostic accuracy in patients with prion disorders. Recently, advances in these tests have led to markedly improved diagnostic sensitivity and reduced assay times. Accordingly, an algorithm has been proposed that entails the use of RT‐QuIC analysis of both sample types to diagnose sporadic Creutzfeldt‐Jakob disease with nearly 100% accuracy. Here we present a multi‐center evaluation (ring trial) of the reproducibility of these improved “second generation” RT‐QuIC assays as applied to these diagnostic specimens. METHODS: Cerebrospinal fluid samples were analyzed from subjects with sporadic Creutzfeldt‐Jakob (n = 55) or other neurological diseases (n = 45) at multiple clinical centers. Olfactory mucosa brushings collected by multiple otolaryngologists were obtained from nine sporadic Creutzfeldt‐Jakob disease cases and 19 controls. These sample sets were initially tested blindly by RT‐QuIC by a coordinating laboratory, recoded, and then sent to five additional testing laboratories for blinded ring trial testing. RESULTS: Unblinding of the results by a third party indicated 98‐100% concordance between the results obtained by the testing of these cerebrospinal fluid and nasal brushings at the six laboratories. INTERPRETATION: This second‐generation RT‐QuIC assay is highly transferrable, reproducible, and therefore robust for the diagnosis of sporadic Creutzfeldt‐Jakob disease in clinical practice. John Wiley and Sons Inc. 2020-11-13 /pmc/articles/PMC7664259/ /pubmed/33185334 http://dx.doi.org/10.1002/acn3.51219 Text en © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Orrú, Christina D.
Groveman, Bradley R.
Foutz, Aaron
Bongianni, Matilde
Cardone, Franco
McKenzie, Neil
Culeux, Audrey
Poleggi, Anna
Grznarova, Katarina
Perra, Daniela
Fiorini, Michele
Liu, Xiaoqin
Ladogana, Anna
Sbriccoli, Marco
Hughson, Andrew G.
Haïk, Stéphane
Green, Alison J.
Geschwind, Michael D.
Pocchiari, Maurizio
Safar, Jiri G.
Zanusso, Gianluigi
Caughey, Byron
Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
title Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
title_full Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
title_fullStr Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
title_full_unstemmed Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
title_short Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
title_sort ring trial of 2nd generation rt‐quic diagnostic tests for sporadic cjd
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664259/
https://www.ncbi.nlm.nih.gov/pubmed/33185334
http://dx.doi.org/10.1002/acn3.51219
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