Abstract | BACKGROUND: METHODS: We collected olfactory epithelium brushings and cerebrospinal fluid samples from patients with and patients without sporadic Creutzfeldt-Jakob disease and tested them using RT-QuIC, an ultrasensitive, multiwell plate-based fluorescence assay involving PrP(CJD)-seeded polymerization of recombinant PrP into amyloid fibrils. RESULTS: The RT-QuIC assays seeded with nasal brushings were positive in 30 of 31 patients with Creutzfeldt-Jakob disease (15 of 15 with definite sporadic Creutzfeldt-Jakob disease, 13 of 14 with probable sporadic Creutzfeldt-Jakob disease, and 2 of 2 with inherited Creutzfeldt-Jakob disease) but were negative in 43 of 43 patients without Creutzfeldt-Jakob disease, indicating a sensitivity of 97% (95% confidence interval [CI], 82 to 100) and specificity of 100% (95% CI, 90 to 100) for the detection of Creutzfeldt-Jakob disease. By comparison, testing of cerebrospinal fluid samples from the same group of patients had a sensitivity of 77% (95% CI, 57 to 89) and a specificity of 100% (95% CI, 90 to 100). Nasal brushings elicited stronger and faster RT-QuIC responses than cerebrospinal fluid (P<0.001 for the between-group comparison of strength of response). Individual brushings contained approximately 10(5) to 10(7) prion seeds, at concentrations several logs10 greater than in cerebrospinal fluid. CONCLUSIONS: In this preliminary study, RT-QuIC testing of olfactory epithelium samples obtained from nasal brushings was accurate in diagnosing Creutzfeldt-Jakob disease and indicated substantial prion seeding activity lining the nasal vault. (Funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and others.).
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Authors | Christina D Orrú, Matilde Bongianni, Giovanni Tonoli, Sergio Ferrari, Andrew G Hughson, Bradley R Groveman, Michele Fiorini, Maurizio Pocchiari, Salvatore Monaco, Byron Caughey, Gianluigi Zanusso |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 371
Issue 6
Pg. 519-29
(Aug 07 2014)
ISSN: 1533-4406 [Electronic] United States |
PMID | 25099576
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Aged
- Brain
(pathology)
- Creutzfeldt-Jakob Syndrome
(diagnosis)
- Epithelium
(chemistry)
- Female
- Fluorescence
- Humans
- Indicator Dilution Techniques
- Male
- Middle Aged
- Nasal Mucosa
(chemistry)
- Prions
(analysis, cerebrospinal fluid)
- Sensitivity and Specificity
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