Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease-Reference-Cited by-同舟云学术

Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease

Published:2024-03-11 Issue:1 Volume:24 Page:
ISSN:1471-2377
Container-title:BMC Neurology
language:en
Short-container-title:BMC Neurol

Author:

Nonaka Toshiaki,Iwasaki Yasushi,Horiuchi Hiroyuki,Satoh Katsuya

Abstract

Abstract Background Human prion diseases (HPDs) are fatal neurodegenerative disorders characterized by abnormal prion proteins (PrPSc). However, the detection of prion seeding activity in patients with high sensitivity remains challenging. Even though real-time quaking-induced conversion (RT-QuIC) assay is suitable for detecting prion seeding activity in a variety of specimens, it shows lower accuracy when whole blood, blood plasma, and blood-contaminated tissue samples are used. In this study, we developed a novel technology for the in vitro amplification of abnormal prion proteins in HPD to the end of enabling their detection with high sensitivity known as the enhanced quaking-induced conversion (eQuIC) assay. Methods Three antibodies were used to develop the novel eQUIC method. Thereafter, SD50 seed activity was analyzed using brain tissue samples from patients with prion disease using the conventional RT-QUIC assay and the novel eQUIC assay. In addition, blood samples from six patients with solitary prion disease were analyzed using the novel eQuIC assay. Results The eQuIC assay, involving the use of three types of human monoclonal antibodies, showed approximately 1000-fold higher sensitivity than the original RT-QuIC assay. However, when this assay was used to analyze blood samples from six patients with sporadic human prion disease, no prion activity was detected. Conclusion The detection of prion seeding activity in blood samples from patients with sporadic prion disease remains challenging. Thus, the development of alternative methods other than RT-QuIC and eQuIC will be necessary for future research.

Funder

Ministry of Health, Labour and Welfare of Japan

Research Committee of Prion Disease and Slow Virus Infection; Research on Policy Planning and Evaluation for Rare and Intractable Diseases

Health and Labour Sciences Research Grants; the Research Committee of Surveillance and Infection Control of Prion Disease

Japan Agency for Medical Research and Development

TaNeDS Funding for Daiichi Sankyo Co., Ltd

Publisher

Springer Science and Business Media LLC

Link

https://link.springer.com/content/pdf/10.1186/s12883-024-03590-7.pdf

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