Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion

Llewelyn, Charlotte; Hewitt, Patricia; Knight, Richard; Amar, Khaled; Cousens, Simon; Mackenzie, Janet; Will, Robert

doi:10.1016/s0140-6736(04)15486-x

Cited by 1,016 publications

(698 citation statements)

References 16 publications

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“…At the present time, vCJD imposes a significant burden on the human blood supply because of the risk of human prion infection through iatrogenic use of blood products [12][13][14]. However, the occurrence of vCJD cases caused by administration of prion-infected human blood has highlighted the realistic opportunity for the development of a blood-based diagnostic test for this condition.…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of vCJD prions in human lymphoid tissue, together with the detection of prion infectivity in the blood of animals with asymptomatic experimental prion disease [10,11], raised the possibility for the potential of blood-borne vCJD transmission. These concerns were realised with the emergence of cases of vCJD in individuals within the U.K. who had received red blood cell concentrates [12][13][14][15]. In addition, abnormal prion protein was detected in a post-mortem spleen sample from a haemophilic patient who had received purified Factor VIII prepared from plasma batches that included donations from individuals who later developed vCJD [12].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Thackray

Andréoletti

Bujdoso

2016

Biochemical Journal

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“…Die vCJK konnte mit der 1986 in Großbritannien aufgetretenen BSE-Epidemie durch Inokulation des BSEAgens auf Makaken in Verbindung gebracht werden (Lasmézas et al 1996a (Llewelyn et al 2004, Peden et al 2004, Wroe et al 2006). …”

Section: Die Neue Variante Der Creutzfeldt-jakob-krankheitunclassified

“…Es sind 4 vCJK-Fälle beschrieben, die wahrscheinlich durch eine Bluttransfusion übertragen wurden (Llewelyn et al 2004, Peden et al 2004, Wroe et al 2006 In bisherigen Studien wurden bisher entweder nicht signifikante Ergebnisse oder verminderte Risiken für den Zusammenhang einer Bluttransfusion mit der sCJK publiziert (Kondo und Kuroiwa 1982, Davanipour et al 1985, Harries-Jones et al 1988, Duijn et al 1998, Zerr et al 2000b, Ward et al 2002und 2008. Zudem wurden bei Patienten mit Hämophilie, die vor der Einführung von rekombinanten Gerinnungsfaktoren Blutprodukten von sehr vielen Spendern ausgesetzt waren, keine CJK-Fälle festgestellt (Evatt et al 1998, Lee et al 1998).…”

Section: Bluttransfusionen Und Blutspendenunclassified

Risikofaktoren der sporadischen Creutzfeldt-Jakob-Krankheit

Kittner

Heinemann

Zerr

2009

Dtsch med Wochenschr

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“…There was no reliable in vitro diagnostic test available until the discovery that TSEs are caused by the conversion of a normal cellular prion protein, PrP C , into the pathogenic, protease resistant scrapie PrP isoform, PrP Sc [31][32][33][34]. In addition, a study in 2004 reported that two patients who received blood from donors who had died from variant Creutzfeldt-Jakob disease [35,36], also developed the disease, indicating that the infectious prion in the blood is a public health concern. Unfortunately, current prion tests are mostly postmortem, invasive, insensitive and nonquantitative.…”

Section: Prion Diseasementioning

confidence: 99%

Non-invasive, ultra-sensitive, high-throughput assays to quantify rare biomarkers in the blood

Freudenberg

Bembas

Greene

et al. 2008

Methods

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Many diseases are easier to treat and control when detected at an early stage of disease progression. Often, disease-related antigens or biomarkers are shed from the primary site and present in the blood. Unfortunately, there are very few tests capable of detecting these rare biomarkers in the blood. A blood test would be very useful to diagnose the disease earlier, monitor effectiveness of treatments, predict recurrence, and monitor recurrence. There is certainly a need to develop assays that are ultrasensitive, non-invasive and high-throughput. Here we describe several highly sensitive immunological assays we have developed to detect rare serum antigens. Initially we created an assay named immunodetection amplified by T7 RNA polymerase (IDAT). To enhance the effectiveness and streamline the procedure, this assay was amended to the facile amplification system termed fluorescent amplification catalyzed by T7 polymerase technique (FACTT). These assays have been used to analyze the tumor antigen HER2 and the prion protein PrP Sc . They can also be applied to other tumor markers or antigens from a variety of diseases such as cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and hepatitis. These tests are not limited to testing only serum, but may also be applicable to detecting biomarkers in tissue, saliva, urine, cerebrospinal fluid, etc. Clearly, the FACTT-based technology represents an important step in the detection of rare molecules in fluids or tissues for a variety of diseases.

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Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion

Cited by 1,016 publications

References 16 publications

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Risikofaktoren der sporadischen Creutzfeldt-Jakob-Krankheit

Non-invasive, ultra-sensitive, high-throughput assays to quantify rare biomarkers in the blood

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