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| Home > Publications Database > Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease. |
| Home > Publications Database > Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease. |
| Journal Article | DZNE-2020-04770 |
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2016
Humana Press
Totowa, NJ
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Please use a persistent id in citations: doi:10.1007/s12035-015-9133-2
Abstract: Real-time quaking-induced conversion (RT-QuIC) allows the amplification of miniscule amounts of scrapie prion protein (PrP(Sc)). Recent studies applied the RT-QuIC methodology to cerebrospinal fluid (CSF) for diagnosing human prion diseases. However, to date, there has not been a formal multi-centre assessment of the reproducibility, validity and stability of RT-QuIC in this context, an indispensable step for establishment as a diagnostic test in clinical practice. In the present study, we analysed CSF from 110 prion disease patients and 400 control patients using the RT-QuIC method under various conditions. In addition, 'blinded' ring trials between different participating sites were performed to estimate reproducibility. Using the previously established cut-off of 10,000 relative fluorescence units (rfu), we obtained a sensitivity of 85% and a specificity of 99%. The multi-centre inter-laboratory reproducibility of RT-QuIC revealed a Fleiss' kappa value of 0.83 (95% CI: 0.40-1.00) indicating an almost perfect agreement. Moreover, we investigated the impact of short-term CSF storage at different temperatures, long-term storage, repeated freezing and thawing cycles and the contamination of CSF with blood on the RT-QuIC seeding response. Our data indicated that the PrP(Sc) seed in CSF is stable to any type of storage condition but sensitive to contaminations with blood (>1250 erythrocytes/μL), which results in a false negative RT-QuIC response. Fresh blood-contaminated samples (3 days) can be rescued by removal of erythrocytes. The present study underlines the reproducibility and high stability of RT-QuIC across various CSF storage conditions with a remarkable sensitivity and specificity, suggesting RT-QuIC as an innovative and robust diagnostic method.
Keyword(s): Adolescent (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Biological Assay: methods (MeSH) ; Creutzfeldt-Jakob Syndrome: blood (MeSH) ; Creutzfeldt-Jakob Syndrome: cerebrospinal fluid (MeSH) ; Creutzfeldt-Jakob Syndrome: diagnosis (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Preservation, Biological (MeSH) ; Reproducibility of Results (MeSH) ; Sensitivity and Specificity (MeSH) ; Time Factors (MeSH) ; Young Adult (MeSH) ; tau Proteins: metabolism (MeSH) ; tau Proteins
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