Prions in the urine of patients with variant Creutzfeldt-Jakob disease

Fabio Moda, Pierluigi Gambetti, Silvio Notari, Luis Concha-Marambio, Marcella Catania, Kyung Won Park, Emanuela Maderna, Silvia Suardi, Stéphane Haïk, Jean Philippe Brandel, James Ironside, Richard Knight, Fabrizio Tagliavini, Claudio Soto

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrPSc). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt-Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt-Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating. METHODS: To investigate whether PrPSc can be detected in the urine of patients with variant Creutzfeldt-Jakob disease, we used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of PrPSc, enabling highly sensitive detection of the protein. We analyzed urine samples from several patients with various transmissible spongiform encephalopathies (variant and sporadic Creutzfeldt-Jakob disease and genetic forms of prion disease), patients with other degenerative or nondegenerative neurologic disorders, and healthy persons. RESULTS: PrPSc was detectable only in the urine of patients with variant Creutzfeldt-Jakob disease and had the typical electrophoretic profile associated with this disease. PrPSc was detected in 13 of 14 urine samples obtained from patients with variant Creutzfeldt-Jakob disease and in none of the 224 urine samples obtained from patients with other neurologic diseases and from healthy controls, resulting in an estimated sensitivity of 92.9% (95% confidence interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to 100.0). The PrPSc concentration in urine calculated by means of quantitative PMCA was estimated at 1×10-16 g per milliliter, or 3×10-21 mol per milliliter, which extrapolates to approximately 40 to 100 oligomeric particles of PrPSc per milliliter of urine. CONCLUSIONS: Urine samples obtained from patients with variant Creutzfeldt-Jakob disease contained minute quantities of PrPSc.

Original languageEnglish
Pages (from-to)530-539
Number of pages10
JournalNew England Journal of Medicine
Volume371
Issue number6
DOIs
Publication statusPublished - Aug 7 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Moda, F., Gambetti, P., Notari, S., Concha-Marambio, L., Catania, M., Park, K. W., Maderna, E., Suardi, S., Haïk, S., Brandel, J. P., Ironside, J., Knight, R., Tagliavini, F., & Soto, C. (2014). Prions in the urine of patients with variant Creutzfeldt-Jakob disease. New England Journal of Medicine, 371(6), 530-539. https://doi.org/10.1056/NEJMoa1404401