Impact of Leucocyte Depletion and Prion Reduction Filters on TSE Blood Borne Transmission

Abstract

The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters.

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

“…The infectious titers that we measured in the whole blood used for the transfusion experiment were lower than 10 ID/ml. These infectious titer values are similar to those established in a previous study in similar animals (VRQ/VRQ sheep) infected with the same scrapie isolate (12,13). These data complement and expand the previously reported results and confirm that the risk of transmitting prion disease by blood transfusion is higher than expected from the measurement of blood infectious titers by the intracerebral inoculation of mice (12).…”

“…This value is lower than the current leukoreduction standard target for red blood cell concentrate (10 6 WBC per unit). This is a likely explanation for the imperfect efficacy of leukoreduction to prevent prion disease transmission by RBC transfusion in sheep TSE models (13,23). Under the hypothesis that the sheep scrapie model is relevant for the evaluation of the vCJD transmission risk by the transfusion route in humans, these results support the contention that RBC leukodepletion is insufficient in the prevention of vCJD blood-borne transmission.…”

“…The intravenous administration of 200 ml fresh crude plasma to sheep transmitted the disease with limited efficacy, but no transmission was observed in animals that received 20 ml of plasma. In contrast, the WBCs displayed an ability similar to that of whole blood in its efficacy at infecting recipient sheep (13,14). These results demonstrated that the ability of blood and blood-derived products to transmit prion disease by the transfusion route does not depend solely on their infectious titer and pointed out the importance that WBC populations might play in the transmission of the disease by the transfusion route (12).…”

“…reduction has had a positive impact on reducing the risk of vCJD transmission by transfusion (10). Various experimental studies carried out in animal models of prion disease have confirmed that leukocyte reduction, as applied in human transfusion medicine, provides significant but incomplete protection against the transmission of prion disease by blood transfusion (13,23).…”

Quantum dots and prion proteins

“…Immunological detection of PrP Sc in peripheral tissues The infectivity studies have shown that prion proteins occurred in low amounts in the peripheral tissues, such as lymphoid organs and blood, 32 already at early stages of the disease, e.g. during the pre-symptomatic period.…”