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. 2023 Mar 23;24(7):6098.
doi: 10.3390/ijms24076098.

Improved Real-Time Quaking Induced Conversion for Early Diagnostics of Creutzfeldt-Jakob Disease in Denmark

Remarh Bsoul  1 , Eva Løbner Lund  1 , Kimberley Burns  2 , Mary Andrews  2 , Neil McKenzie  2 , Alison Green  2 , Aušrinė Areškevičiūtė  1
Affiliations

Improved Real-Time Quaking Induced Conversion for Early Diagnostics of Creutzfeldt-Jakob Disease in Denmark

Remarh Bsoul et al. Int J Mol Sci. .

Abstract

Cerebrospinal fluid-based real-time quaking-induced conversion (CSF RT-QuIC) is currently the most prominent method for early detection of sporadic Creutzfeldt-Jakob disease (sCJD), the most common prion disease. CSF RT-QuIC delivers high sensitivity (>90%) and specificity (100%), which has been demonstrated by large ring-trial studies testing probable and definitive sCJD cohorts. Following the inclusion of CSF RT-QuIC in the revised European CJD Surveillance Network diagnostic criteria for sCJD, it has become a standard diagnostic procedure in many prion disease reference or surveillance centers around the world. In this study, we present the implementation of the second-generation CSF RT-QuIC (commonly known as Improved QuIC or IQ) at the Danish Reference Center for Prion Diseases (DRCPD). The method's sensitivity and specificity were evaluated and validated by analyzing 63 CSF samples. These 63 samples were also analyzed at the National CJD Research and Surveillance Unit (NCJDRSU), based at the University of Edinburgh, UK; analysis was carried out using the first generation or previous CSF RT-QuIC method (PQ). The sensitivity and specificity of PQ during tests at the NCJDRSU were 92% and 100%, respectively. Using these 63 CSF samples, the agreement between the two RT-QuIC generations at DRCPD and NCJDRSU prion laboratories was 100%.

Keywords: Creutzfeldt–Jakob disease—CJD; RT-QuIC; cerebrospinal fluid—CSF; early diagnostics; improved real-time quaking-induced conversion—IQ; neurodegenerative protein misfolding diseases; prion disease; prions; recombinant PrP production and storage.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) IQ kinetics, time, and intensity with 30 µL CSF. Green is a mean of the two best replicates in a quadruple setup with error bars (95% confidence interval). Red is a mean of all negative replicates in a quadruple setup. Dotted line represents the RFU cut-off value for a positive replicate. (b) CSF volume-dependent IQ kinetics, time, and intensity. Blue and Green curves represent mean RFU of 15 μL and 30 μL replicates (n = 144) of CSF samples from probable sCJD patients. Error bars depicts 95% confidence interval. Red curve represents a mean of quadruplicates of 23 CSF samples from non-CJD patients tested at 15 µL and 30 µL. Dotted line represents the RFU cut-off value for a positive replicate.
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Supplementary concepts

Grants and funding

A.G., N.M., M.A. and K.B. were funded by the Policy Research Programme, Department of Health and Social Care and the Scottish Government [The National CJD Research and Surveillance Unit (NCJDRSU), PR-ST-0614-00008_18.