Medicine:Real-time quaking-induced conversion

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Short description: Highly sensitive assay for prion detection

Real-time quaking-induced conversion (RT-QuIC) is a highly sensitive assay for prion detection.[1]

Technique

The "quaking" in the name of the technique refers to the fact that samples in the RT-QuIC assay are literally subjected to shaking. This action breaks apart aggregates of prion protein (PrP) that are then further incubated, amplifying the amount of misfolded PrP to detectable levels.[2][3]

It is "an early, rapid and specific assay for prion diseases". It can sample multiple sample types, such as cerebrospinal fluid (CSF), brain, lymph nodes, blood, muscle, and skin, and so it is applicable to scrapie in sheep, chronic wasting disease (CWD) in cervids, bovine spongiform encephalopathy (BSE) in cows and sporadic Creutzfeldt–Jakob disease in humans, amongst others.[4]

The RT-QuIC assay uses in excess recombinantly produced normally folded prions, often a truncated Syrian Hamster protein, amino acids 90-231. Samples suspected of containing misfolded prions are added, leading to misfolding and aggregation of normally folded prions. These protein aggregates can be detected by thioflavin T visible spectrum fluorescence detection.[5][6][7] The Centers for Disease Control and Prevention includes a positive RT-QuIC result in its diagnostic criteria for the probable diagnosis of sCJD.[8]

RT-QuIC assays can also be used to test for scrapie, BSE, CWD, and sCJD. Various procedures can improve sensitivity and specificity. Iron oxide metal extraction (IOME) uses the natural metal affinity of the prion protein; a sample is incubated with magnetic beads, which bind to the prion protein. The prion-rich bead fraction is subsequently harvested and tested.[9]

Commonly tested tissues are brain homogenates and lymph tissues, however prions have been detected in skin and blood samples.[10][11][12] Certain tissues can be difficult to test for prions. For example, blood samples tend to have low levels of circulating intracellular prions, as well as inhibitors.[13]

See also

References

  1. ↑ Zerr, Inga; Cramm, Maria; da Silva Correia, Susana Margarida; Zafar, Saima; Villar-Piqué, Anna; Llorens, Franc; Schmitz, Matthias (2020-11-19). "Optimization of the Real-Time Quaking-Induced Conversion Assay for Prion Disease Diagnosis". Frontiers in Bioengineering and Biotechnology 8: 586890. doi:10.3389/fbioe.2020.586890. ISSN 2296-4185. PMID 33330419. 
  2. ↑ Lewczuk, Piotr; Riederer, Peter; O’Bryant, Sid E.; Verbeek, Marcel M.; Dubois, Bruno; Visser, Pieter Jelle; Jellinger, Kurt A.; Engelborghs, Sebastiaan et al. (27 October 2017). "Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry". The World Journal of Biological Psychiatry 19 (4): 244–328. doi:10.1080/15622975.2017.1375556. PMID 29076399. 
  3. ↑ Cramm, Maria; Schmitz, Matthias; Karch, André; Mitrova, Eva; Kuhn, Franziska; Schroeder, Bjoern; Raeber, Alex; Varges, Daniela et al. (1 April 2015). "Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease". Molecular Neurobiology 53 (3): 1896–1904. doi:10.1007/s12035-015-9133-2. PMID 25823511. 
  4. ↑ Atarashi, R.; Sano, K.; Satoh, K.; Nishida, N. (2011). "Real-time quaking-induced conversion: A highly sensitive assay for prion detection". Prion 5 (3): 150–3. doi:10.4161/pri.5.3.16893. PMID 21778820. 
  5. ↑ "Chronic wasting disease of cervids: current knowledge and future perspectives". Annual Review of Animal Biosciences 3: 305–25. 2015. doi:10.1146/annurev-animal-022114-111001. PMID 25387112. 
  6. ↑ "Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion". Nature Medicine 17 (2): 175–78. February 2011. doi:10.1038/nm.2294. PMID 21278748. http://naosite.lb.nagasaki-u.ac.jp/dspace/bitstream/10069/25642/1/NatMEd17_175.pdf. 
  7. ↑ "A test for Creutzfeldt–Jakob disease using nasal brushings". The New England Journal of Medicine 371 (6): 519–29. August 2014. doi:10.1056/NEJMoa1315200. PMID 25099576. 
  8. ↑ "CDC's Diagnostic Criteria for Creutzfeldt–Jakob Disease (CJD), 2018". Centers for Disease Control and Prevention. September 17, 2018. https://www.cdc.gov/prions/cjd/diagnostic-criteria.html. "Adapted from: a) Global surveillance, diagnosis, and therapy of human transmissible spongiform encephalopathies: Report of a WHO consultation, February 1998, Geneva, Switzerland; b) Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 2009, 132; 2659–2668; and c) National CJD Research & Surveillance Unit. Protocol: Surveillance of CJD in the UK. Item c accessed 15 Aug 2018." 
  9. ↑ Denkers, N. D., Henderson, D. M., Mathiason, C. K. & Hoover, E. A. Enhanced prion detection in biological samples by magnetic particle extraction and real-time quaking-induced conversion. J. Gen. Virol. 97, 2023–2029. https://doi.org/10.1099/jgv.0.000515 (2016)
  10. ↑ Mammana, A., Baiardi, S., Rossi, M., Franceschini, A., Donadio, V., Capellari, S., Caughey, B. and Parchi, P. (2020), Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients. Ann Clin Transl Neurol, 7: 559-564. https://doi.org/10.1002/acn3.51000
  11. ↑ Concha-Marambio L, Pritzkow S, Moda F, et al. Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease. Sci Transl Med. 2016;8(370):370ra183. doi:10.1126/scitranslmed.aaf6188
  12. ↑ Orrú CD, Yuan J, Appleby BS, Li B, Li Y, Winner D, Wang Z, Zhan YA, Rodgers M, Rarick J, Wyza RE, Joshi T, Wang GX, Cohen ML, Zhang S, Groveman BR, Petersen RB, Ironside JW, Quiñones-Mateu ME, Safar JG, Kong Q, Caughey B, Zou WQ. Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease. Sci Transl Med. 2017 Nov 22;9(417):eaam7785. doi: 10.1126/scitranslmed.aam7785. PMID: 29167394; PMCID: PMC5744860
  13. ↑ Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion, Christina D. Orrú, Jason M. Wilham, Lynne D. Raymond, Franziska Kuhn, Björn Schroeder, Alex J. Raeber, Byron Caughey mBio May 2011, 2 (3) e00078-11; DOI: 10.1128/mBio.00078-11



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