Mononucleated Blood Cell Populations Display Different Abilities To Transmit Prion Disease by the Transfusion Route

Abstract

Previous experiments carried out in a sheep scrapie model demonstrated that the transfusion of 200 l of prion-infected whole blood has an apparent 100% efficacy for disease transmission. These experiments also indicated that, despite the apparent low infectious titer, the intravenous administration of white blood cells (WBC) resulted in efficient disease transmission. In the study presented here, using the same transmissible spongiform encephalopathy (TSE) animal model, our aim was to determine the minimal number of white blood cells and the specific abilities of mononucleated cell populations to transmit scrapie by the transfusion route. Our results confirmed that the transfusion of 100 l, but not 10 l, of fresh whole blood collected in asymptomatic scrapie-infected donor sheep can transmit the disease. The data also show that the intravenous administration of 10 5WBCs is sufficient to cause scrapie in recipient sheep. Cell-sorted CD45R ؉ (predominantly B lymphocytes), CD4 ؉ /CD8 ؉ (T lymphocytes), and CD14؉ (monocytes/macrophages) blood cell subpopulations all were shown to contain prion infectivity by bioassays in ovine PrP transgenic mice. However, while the intravenous administration of 10 6 CD45 ؉ or CD4 ؉ /8 ؉ living cells was able to transmit the disease, similar numbers of CD14؉ cells failed to infect the recipients. These data support the contention that mononucleated blood cell populations display different abilities to transmit TSE by the transfusion route. They also represent an important input for the risk assessment of blood-borne prion disease transmission and for refining the target performance of leukoreduction processes that currently are applied to mitigate the transmission risk in transfusion medicine. IMPORTANCEInterindividual variant Creutzfeldt-Jakob disease (vCJD) transmission through blood and blood-derived products is considered a major public health issue in transfusion medicine. Over the last decade, TSE in sheep has emerged as a relevant model for assessing the blood-borne vCJD transmission risk. In this study, using a sheep TSE model, we characterized the ability of different peripheral blood mononucleated cell populations to infect TSE-free recipients by the transfusion route. Our results indicate that as little as 10 5 WBC and 100 l of blood collected from asymptomatic scrapie infected animals can transmit the disease. They also demonstrate unambiguously that peripheral blood mononuclear cell subpopulations display dramatically different abilities to transmit the disease. These data represent an important input for the risk assessment of blood-borne prion disease transmission and for refining the target performance of leukoreduction processes that currently are applied to mitigate the transmission risk in transfusion medicine.

Expression and functions of cellular prion proteins in immunocytes

“…4 It has also been demonstrated that intravenous infusion of white blood cell (WBC) products from preclinical scrapie-infected sheep can spread TSE, with a minimum pathogenic titre of 10 5 WBCs or 100 μL of whole blood, lower than previous leukoreduction standards for red blood cell (RBC) concentrates in transfusion medicine. 5 These findings indicate that the host immune system can play a significant role in the invasion and transmission of TSE. PrP C , encoded by the PRNP gene and consisting of approximately 250 amino acid residues, is a highly conserved membrane-bound glycoprotein anchored by glycosylphosphatidylinositol (GPI).…”

“…While it was generally believed that the effects of TSE were limited to the central nervous system (CNS); subsequent studies have demonstrated that PrP Sc primarily aggregates and replicates in the secondary lymphoid organs (SLOs) during host invasion, after which they migrate to the CNS . It has also been demonstrated that intravenous infusion of white blood cell (WBC) products from preclinical scrapie‐infected sheep can spread TSE, with a minimum pathogenic titre of 10 5 WBCs or 100 μL of whole blood, lower than previous leukoreduction standards for red blood cell (RBC) concentrates in transfusion medicine . These findings indicate that the host immune system can play a significant role in the invasion and transmission of TSE.…”

Creutzfeldt‐Jakob disease and blood transfusion safety

“…In sheep transfused with blood components from BSE‐infected donor sheep, the highest transmission rates were found in those inoculated with buffy coat fractions . In the sheep scrapie model, the minimum number of white blood cells capable of transmitting scrapie following intravenous administration was 10 5 . The distribution of infectivity among specific subsets of WBC (e.g.…”

“…The distribution of infectivity among specific subsets of WBC (e.g. lymphocytes, monocytes, granulocytes) has not been clearly established, but all these cell types may be capable of transmitting infection to varying extents .…”

Problems with precaution: the transfusion medicine experience

“…The primary driver for the maintenance of the vCJD policies is a theoretical concern for a genetically at-risk population who may develop the condition at a later time, harboring infectious prions in lymphatic tissues (Wilson and Ricketts 2006a). There is no blood or urine test for the identification of vCJD, although this remains an area of active research interest (Edgeworth et al 2011;Moda et al 2014;Douet et al 2016).…”