RT-QuIC detection of chronic wasting disease prion in platelet samples of white-tailed deer

Journal Article · 23 April 2024 · BMC Veterinary Research

DOI: https://doi.org/10.1186/s12917-024-04005-y · OSTI ID:2407057

Kobashigawa, Estela ^[1]; Russell, Sherri ^[2]; Zhang, Michael Z. ^[1]; Sinnott, Emily A. ^[2]; Connolly, Michael ^[3]; Zhang, Shuping ^[1]

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1. University of Missouri, Columbia, MO (United States)
2. Missouri Department of Conservation, Jefferson City, MO (United States)
3. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Chronic wasting disease (CWD) is a prion disease of captive and free-ranging cervids. Currently, a definitive diagnosis of CWD relies on immunohistochemistry detection of PrP^Sc in the obex and retropharyngeal lymph node (RPLN) of the affected cervids. For high-throughput screening of CWD in wild cervids, RPLN samples are tested by ELISA followed by IHC confirmation of positive results. Recently, real-time quacking-induced conversion (RT-QuIC) has been used to detect CWD positivity in various types of samples. To develop a blood RT-QuIC assay suitable for CWD diagnosis, this study evaluated the assay sensitivity and specificity with and without ASR1-based preanalytical enrichment and NaI as the main ionic component in assay buffer. A total of 23 platelet samples derived from CWD-positive deer (ELISA +/IHC +) and 30 platelet samples from CWD-negative (ELISA-) deer were tested. The diagnostic sensitivity was 43.48% (NaCl), 65.22% (NaI), 60.87% (NaCl-ASR1) or 82.61% (NaI-ASR1). The diagnostic specificity was 96.67% (NaCl), 100% (NaI), 100% (NaCl-ASR1), or 96.67% (NaI-ASR1). The probability of detecting CWD prion in platelet samples derived from CWD-positive deer was 0.924 (95% CRI: 0.714, 0.989) under NaI-ASR1 experimental condition and 0.530 (95% CRI: 0.156, 0.890) under NaCl alone condition. The rate of amyloid formation (RFA) was greatest under the NaI-ASR1 condition at 10^-2 (0.01491, 95% CRI: 0.00675, 0.03384) and 10^-3 (0.00629, 95% CRI: 0.00283, 0.01410) sample dilution levels. Incorporation of ASR1-based preanalytical enrichment and NaI as the main ionic component signifcantly improved the sensitivity of CWD RT-QuIC on deer platelet samples. Blood test by the improved RT-QuIC assay may be used for antemortem and postmortem diagnosis of CWD.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES); Missouri Department of Conservation
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 2407057
• Journal Information: BMC Veterinary Research, Journal Name: BMC Veterinary Research Journal Issue: 1 Vol. 20; ISSN 1746-6148
• Publisher: BioMed CentralCopyright Statement
• Country of Publication: United States
• Language: English