Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD
Abstract 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 th...
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Wiley
2020-11-01
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Series: | Annals of Clinical and Translational Neurology |
Online Access: | https://doi.org/10.1002/acn3.51219 |
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doaj-bb5874f625804d7ba24ed64e6f1053e6 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christina D. Orrú Bradley R. Groveman Aaron Foutz Matilde Bongianni Franco Cardone Neil McKenzie Audrey Culeux Anna Poleggi Katarina Grznarova Daniela Perra Michele Fiorini Xiaoqin Liu Anna Ladogana Marco Sbriccoli Andrew G. Hughson Stéphane Haïk Alison J. Green Michael D. Geschwind Maurizio Pocchiari Jiri G. Safar Gianluigi Zanusso Byron Caughey |
spellingShingle |
Christina D. Orrú Bradley R. Groveman Aaron Foutz Matilde Bongianni Franco Cardone Neil McKenzie Audrey Culeux Anna Poleggi Katarina Grznarova Daniela Perra Michele Fiorini Xiaoqin Liu Anna Ladogana Marco Sbriccoli Andrew G. Hughson Stéphane Haïk Alison J. Green Michael D. Geschwind Maurizio Pocchiari Jiri G. Safar Gianluigi Zanusso Byron Caughey Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJD Annals of Clinical and Translational Neurology |
author_facet |
Christina D. Orrú Bradley R. Groveman Aaron Foutz Matilde Bongianni Franco Cardone Neil McKenzie Audrey Culeux Anna Poleggi Katarina Grznarova Daniela Perra Michele Fiorini Xiaoqin Liu Anna Ladogana Marco Sbriccoli Andrew G. Hughson Stéphane Haïk Alison J. Green Michael D. Geschwind Maurizio Pocchiari Jiri G. Safar Gianluigi Zanusso Byron Caughey |
author_sort |
Christina D. Orrú |
title |
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_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_sort |
ring trial of 2nd generation rt‐quic diagnostic tests for sporadic cjd |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2020-11-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1002/acn3.51219 |
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doaj-bb5874f625804d7ba24ed64e6f1053e62021-05-02T22:55:09ZengWileyAnnals of Clinical and Translational Neurology2328-95032020-11-017112262227110.1002/acn3.51219Ring trial of 2nd generation RT‐QuIC diagnostic tests for sporadic CJDChristina D. Orrú0Bradley R. Groveman1Aaron Foutz2Matilde Bongianni3Franco Cardone4Neil McKenzie5Audrey Culeux6Anna Poleggi7Katarina Grznarova8Daniela Perra9Michele Fiorini10Xiaoqin Liu11Anna Ladogana12Marco Sbriccoli13Andrew G. Hughson14Stéphane Haïk15Alison J. Green16Michael D. Geschwind17Maurizio Pocchiari18Jiri G. Safar19Gianluigi Zanusso20Byron Caughey21Laboratory of Persistent Viral Diseases Rocky Mountain LaboratoriesNational Institute for Allergy and Infectious DiseasesNational Institutes of Health Hamilton MontanaUSALaboratory of Persistent Viral Diseases Rocky Mountain LaboratoriesNational Institute for Allergy and Infectious DiseasesNational Institutes of Health Hamilton MontanaUSADepartments of Pathology and Neurology Case Western Reserve University Cleveland OhioUSADepartment of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona ItalyDepartment of Neuroscience Istituto Superiore di Sanità Rome ItalyNational CJD Research and Surveillance Unit Centre for Clinical Brain Sciences School of Clinical Sciences University of Edinburgh Edinburgh United KingdomSorbonne UniversitéINSERMCNRSUMR 7225Institut du Cerveau et de la Moelle épinièreICM Paris FranceDepartment of Neuroscience Istituto Superiore di Sanità Rome ItalySorbonne UniversitéINSERMCNRSUMR 7225Institut du Cerveau et de la Moelle épinièreICM Paris FranceDepartment of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona ItalyDepartments of Pathology and Neurology Case Western Reserve University Cleveland OhioUSADepartment of Neuroscience Istituto Superiore di Sanità Rome ItalyDepartment of Neuroscience Istituto Superiore di Sanità Rome ItalyLaboratory of Persistent Viral Diseases Rocky Mountain LaboratoriesNational Institute for Allergy and Infectious DiseasesNational Institutes of Health Hamilton MontanaUSASorbonne UniversitéINSERMCNRSUMR 7225Institut du Cerveau et de la Moelle épinièreICM Paris FranceNational CJD Research and Surveillance Unit Centre for Clinical Brain Sciences School of Clinical Sciences University of Edinburgh Edinburgh United KingdomDepartment of Neurology, Memory and Aging Center University of California San Francisco San Francisco CaliforniaUSADepartment of Neuroscience Istituto Superiore di Sanità Rome ItalyDepartments of Pathology and Neurology Case Western Reserve University Cleveland OhioUSADepartment of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona ItalyLaboratory of Persistent Viral Diseases Rocky Mountain LaboratoriesNational Institute for Allergy and Infectious DiseasesNational Institutes of Health Hamilton MontanaUSAAbstract 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.https://doi.org/10.1002/acn3.51219 |