Transmission of prion diseases by blood transfusion

Hunter, Nora; Foster, James D.; Chong, Angela; McCutcheon, Sandra; Parnham, David; Eaton, Samantha L.; MacKenzie, Calum; Houston, Fiona

doi:10.1099/0022-1317-83-11-2897

Cited by 462 publications

(336 citation statements)

References 30 publications

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“…Prions are present in the blood of infected animals, since the disease has been shown to be transmitted by transfusionÅ [12].Å HoweverÅ becauseÅ ofÅ theÅ highÅ specificÅ infectivity of purified prion preparations (as high as 10 11 infectious units (IU) per milligram of protein purified fromÅ SyrianÅ hamstersÅ inoculatedÅ withÅ strainÅ 263K)Å [13], and the fact that in rodent models of TSE, blood contains 5 to 10 IU/mL in preclinical animals and a maximum of about 100 IU/mL at the time of disease onset, it has been estimated that blood contains about 0.05Å toÅ 1.0Å pgÅ (30Å -Å 625Å amol)Å ofÅ PrP ScÅ perÅ mLÅ [14].…”

mentioning

confidence: 99%

Mass spectrometric detection of attomole amounts of the prion protein by nanoLC/MS/MS

Onisko¹,

Dynin²,

Requena

et al. 2007

J. Am. Soc. Mass Spectrom.

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Sensitive quantitation of prions in biological samples is an extremely important and challenging analytical problem. Prions are the cause of several fatal neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). At this time, there are no methods to diagnose TSEs in live animals or to assure a prion-free blood supply for humans. Prions have been shown to be present in blood by transfusion experiments, but based on the amount of infectivity found in these types of experiments, the amount of misfolded prion protein in blood is estimated to be only 30 to 625 amol/mL. More sensitive detection of prions in brain would allow earlier detection of disease and assure a safer food supply. We studied quantitation of the prion protein by use of nanoscale liquid chromatography coupled to a tandem mass spectrometer using the multiple reaction monitoring mode of operation. We developed a method based on the detection of VVEQMCTTQYQK obtained by reduction, alkylation, and digestion with trypsin of the prion protein.

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mentioning

confidence: 99%

Mass spectrometric detection of attomole amounts of the prion protein by nanoLC/MS/MS

Onisko¹,

Dynin²,

Requena

et al. 2007

J. Am. Soc. Mass Spectrom.

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“…Studies in ruminants have analysed bioassays of autologous whole or fractionated blood by the intravenous route [19,20]. These experimental transfusion studies have confirmed that all blood fractions prepared by protocols similar to those used in transfusion medicine can transmit prion disease [23,24]. In addition, prion transmission by transfusion of cellular blood fractions was not solely dependent on their infectious titre since prion disease was more efficiently transmitted with viable rather than non-viable leukocytes [20].…”

Section: Introductionmentioning

confidence: 92%

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Thackray

Andréoletti

Bujdoso

2016

Biochemical Journal

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In pursuit of a tractable bioassay to assess blood prion infectivity, we have generated prion protein (PrP) transgenic Drosophila, which show a neurotoxic phenotype in adulthood after exposure to exogenous prions at the larval stage. Here, we determined the sensitivity of ovine PrP transgenic Drosophila to ovine prion infectivity by exposure of these flies to a dilution series of scrapie-infected sheep brain homogenate. Ovine PrP transgenic Drosophila showed a significant neurotoxic response to dilutions of 10−2 to 10−10 of the original scrapie-infected sheep brain homogenate. Significantly, we determined that this prion-induced neurotoxic response in ovine PrP transgenic Drosophila was transmissible to ovine PrP transgenic mice, which is indicative of authentic mammalian prion detection by these flies. As a consequence, we considered that PrP transgenic Drosophila were sufficiently sensitive to exogenous mammalian prions to be capable of detecting prion infectivity in the blood of scrapie-infected sheep. To test this hypothesis, we exposed ovine PrP transgenic Drosophila to scrapie-infected plasma, a blood fraction notoriously difficult to assess by conventional prion bioassays. Notably, pre-clinical plasma from scrapie-infected sheep induced neurotoxicity in PrP transgenic Drosophila and this effect was more pronounced after exposure to samples collected at the clinical phase of disease. The neurotoxic phenotype in ovine PrP transgenic Drosophila induced by plasma from scrapie-infected sheep was transmissible since head homogenate from these flies caused neurotoxicity in recipient flies during fly-to-fly transmission. Our data show that PrP transgenic Drosophila can be used successfully to bioassay prion infectivity in blood from a prion-diseased mammalian host.

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“…[46] is of particular relevance since the tissue distribution of both infectivity and PrP Sc in sheep with BSE and scrapie closely resembles that in vCJD in humans. Furthermore, the route of infection in this experimental model (oral challenge with BSE-infected brain tissue) is in keeping with the postulated (but not proven) route of BSE infection in vCJD.…”

Section: Evidence For Infectivity In Blood In Prion Diseasesmentioning

confidence: 97%

“…A preliminary result of positive transmission of BSE by blood transfusion from a sheep in the preclinical stage of the disease [43] attracted some criticism in view of the lack of control data [44,45]. However, a recent updated publication has reported that an additional BSE transmission by transfusion of whole blood from a donor animal during the preclinical stage of infection has occurred, with two further animals showing early signs of BSE, having been transfused with whole blood taken when the donors were themselves in the clinical phase of BSE [46]. Assuming that the two recent suspect cases are confirmed, the minimum rate of BSE infection by transfusion in this series is approximately 17%.…”

Section: Evidence For Infectivity In Blood In Prion Diseasesmentioning

confidence: 99%

“…Assuming that the two recent suspect cases are confirmed, the minimum rate of BSE infection by transfusion in this series is approximately 17%. The same study [46] also investigated the possibility of scrapie transmission by blood transfusion, which was achieved at a rate of around 19% at the time of publication. Of particular interest, one positive scrapie transmission occurred in a sheep transfused with buffy coat taken at the clinical endpoint of disease from the donor.…”

Section: Evidence For Infectivity In Blood In Prion Diseasesmentioning

confidence: 99%

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Variant Creutzfeldt–Jakob disease and its transmission by blood

Ironside

Head

2003

Journal of Thrombosis and Haemostasis

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Summary. Variant Creutzfeldt–Jakob disease (vCJD) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (BSE). vCJD differs from all other human prion diseases in that the disease‐associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell‐associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease‐associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease‐associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD.

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Transmission of prion diseases by blood transfusion

Cited by 462 publications

References 30 publications

Mass spectrometric detection of attomole amounts of the prion protein by nanoLC/MS/MS

Mass spectrometric detection of attomole amounts of the prion protein by nanoLC/MS/MS

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Variant Creutzfeldt–Jakob disease and its transmission by blood

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