Detection of prions in the urine of patients affected by sporadic Creutzfeldt-Jakob disease.


Journal

Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278

Informations de publication

Date de publication:
10 Oct 2023
Historique:
received: 20 09 2023
accepted: 25 09 2023
medline: 10 10 2023
pubmed: 10 10 2023
entrez: 10 10 2023
Statut: aheadofprint

Résumé

Currently, it is unknown whether infectious prions are present in peripheral tissues and biological fluids of patients affected by sporadic Creutzfeldt-Jakob disease (sCJD), the most common prion disorder in humans. This represents a potential risk for inter-individual prion infection. The main goal of this study was to evaluate the presence of prions in urine of patients suffering from the major subtypes of sCJD. Urine samples from sCJD patients spanning the six major subtypes were tested. As controls, we used urine samples from people affected by other neurological or neurodegenerative diseases as well as healthy controls. These samples were analyzed blinded. The presence of prions was detected by a modified version of the PMCA technology, specifically optimized for high sensitive detection of sCJD prions. The PMCA assay was first optimized to detect low quantities of prions in diluted brain homogenates from patients affected by all subtypes of sCJD spiked into healthy urine. Twenty-nine of the 81 patients affected by sCJD analyzed in this study were positive by PMCA testing, whereas none of the 160 controls showed any signal. These results indicate a 36% sensitivity and 100% specificity. The subtypes with the highest positivity rate were VV1 and VV2, which combined account for about 15-20% of all sCJD cases, and no detection was observed in MV1 and MM2. Our findings indicate that potentially infectious prions are secreted in urine of some sCJD patients, suggesting a possible risk for inter-individual transmission. Prion detection in urine might be used as a noninvasive preliminary screening test to detect sCJD.

Identifiants

pubmed: 37814583
doi: 10.1002/acn3.51919
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : P01 AI077774
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106705
Pays : United States

Informations de copyright

© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

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Auteurs

Sandra Pritzkow (S)

Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.

Frank Ramirez (F)

Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.

Adam Lyon (A)

Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.

Paul E Schulz (PE)

Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.

Brian Appleby (B)

Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.

Fabio Moda (F)

Division of Neurology 5 - Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Santiago Ramirez (S)

Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.

Silvio Notari (S)

Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.

Pierluigi Gambetti (P)

Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.

Claudio Soto (C)

Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.

Classifications MeSH