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Title: Classical scrapie prions in ovine blood are associated with B lymphocytes and platelets-rich plasma

Author
item DASSANAYAKE, ROHANA - Washington State University
item Schneider, David
item Truscott, Thomas
item YOUNG, ALAN - South Dakota State University
item Zhuang, Dongyue
item O'Rourke, Katherine

Submitted to: BioMed Central (BMC) Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2011
Publication Date: 11/23/2011
Citation: Dassanayake, R.P., Schneider, D.A., Truscott, T.C., Young, A.J., Zhuang, D., Orourke, K.I. 2011. Classical scrapie prions in ovine blood are associated with B lymphocytes and platelets-rich plasma. BioMed Central (BMC) Veterinary Research. 7:75.

Interpretive Summary: Classical scrapie is a naturally occurring fatal brain disease of sheep and goats which is caused by prions, a novel class of infectious agent. Presently, laboratory diagnosis of scrapie disease in live animals is limited to the detection of a misfolded form of prion protein (PrP-Sc) in biopsies of certain lymphoid tissues. Although collection of a blood sample for testing would be more convenient and allow more opportunity for repeat testing, the sensitivity for detecting PrP-Sc in blood samples has been unsuitably low. In the research setting, we have used the more sensitive detection of infectivity to better define which parts of the blood contain prions. Our results show that scrapie prions are primarily associated with certain types of circulating immune cells and with platelet-rich, but not platelet-depleted, plasma. The results of this study suggest it might be possible to improve the sensitivity for detecting PrP-Sc in blood samples by developing efficient methods to concentrate these parts of the blood sample prior to testing.

Technical Abstract: Classical scrapie is a naturally occurring fatal brain disease of sheep and goats which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood sample for live-animal testing would be convenient, the sensitivity of current methods for detecting PrP-Sc in blood samples has been unsuitably low. Therefore, the objective of this study was to further define the blood components which harbor prions in sheep, knowledge which might be used to improve the sensitivity of blood-based assays through sample enrichment. The infectious components of blood were detected using a lamb transfusion model and either whole blood or defined components of blood (peripheral blood mononuclear cells [PBMCs], B lymphocytes, and platelet-rich plasma or platelet-depleted plasma) derived from sheep with preclinical as well as clinical disease. Disease transmission was monitored by biopsy of the rectal mucosa and by post-mortem analyses. Consistent with previous reports, prions were detected in whole blood and in buffy coat fraction. Furthermore, prions were associated with PBMCs, circulating B lymphocytes (CD72+), a B lymphocyte subpopulation (CD21+), and with platelet-rich, but not platelet-depleted, plasma. The results suggest enrichment of blood-based assays with B lymphocytes and platelet-rich, but not platelet-depleted, blood fractions might improve the diagnostic sensitivity of blood-based tests for classical scrapie disease in sheep.