Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands

Gregori, Luisa; Lambert, Brian C.; Gurgel, Patrick V.; Gheorghiu, Liliana; Edwardson, Peter A.D.; Lathrop, Julia Tait; MacAuley, Claudia; Carbonell, Ruben G.; Burton, Steven J.; Hammond, David J.; Rohwer, Robert G.

doi:10.1111/j.1537-2995.2006.00865.x

Cited by 63 publications

(77 citation statements)

References 9 publications

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“…Moreover, the infectivity associated with S HS was not removed by leukodepletion from whole blood and red blood cells, further confirming its soluble nature and its presumed biophysical similarity to the endogenous soluble plasma-associated infectivity [10]. This soluble S HS -associated infectivity could represent the same form of prion infectivity previously described by Gregori et al [16,17] as the portion of the TSE infectivity present in a brain spike that could not be removed during validation studies for prion removal from blood.…”

Section: Introductionsupporting

confidence: 73%

Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster

Abdel‐Haq

2015

Arch Virol

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The high-speed supernatant (S(HS)) of scrapie-infected hamster brain homogenate contains a soluble infectivity similar to that of the plasma that escapes leukodepletion and can transmit prion infection. This recent finding highlights the fact that soluble prion infectivity could be relevant for prion disease propagation and progression. PrP(Sc) is essential in prion disease pathogenesis, but little to nothing is known about the PrP(Sc) species that may be associated with this form of prion infectivity. Scrapie-infected hamster plasma and S(HS) were subjected to biochemical analysis, and the results demonstrate for the first time that soluble infectivity is associated with a water-soluble PrP(Sc) species with substantially different properties from classical PrP(Sc), the concentration of which seems to correlate with the magnitude and efficiency of the soluble infectivity. Such characteristics suggest that this species might represent the soluble prion agent itself or its vehicle, highlighting the need to adequately revise the strategies involved in prion removal, diagnosis, and therapy.

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Section: Introductionsupporting

confidence: 73%

Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster

Abdel‐Haq

2015

Arch Virol

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“…In our laboratory the concentration of 263K scrapie in the brains of hamsters in the late stages of symptomatic disease is consistently between 1 and 2×10 10 Infectious Dose 50 /g of brain [23]. In the absence of amplification, a 10 10 dilution of 263K brain would contain 1 ID 50 /ml giving a probability of infection of 0.05 from a 50 µl inoculation [23]. Nevertheless, all animals inoculated with PMCA products formed in the presence or absence of beads developed clinical disease with the mean value of endpoint 108.6±3.9 or 114.2±6.3 days post inoculation, respectively (Fig.…”

Section: Resultsmentioning

confidence: 79%

“…The final dilution of the initial 263K brain material was 10 10 fold. In our laboratory the concentration of 263K scrapie in the brains of hamsters in the late stages of symptomatic disease is consistently between 1 and 2×10 10 Infectious Dose 50 /g of brain [23]. In the absence of amplification, a 10 10 dilution of 263K brain would contain 1 ID 50 /ml giving a probability of infection of 0.05 from a 50 µl inoculation [23].…”

Section: Resultsmentioning

confidence: 89%

Highly Efficient Protein Misfolding Cyclic Amplification

et al. 2011

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Protein misfolding cyclic amplification (PMCA) provides faithful replication of mammalian prions in vitro and has numerous applications in prion research. However, the low efficiency of conversion of PrPC into PrPSc in PMCA limits the applicability of PMCA for many uses including structural studies of infectious prions. It also implies that only a small sub-fraction of PrPC may be available for conversion. Here we show that the yield, rate, and robustness of prion conversion and the sensitivity of prion detection are significantly improved by a simple modification of the PMCA format. Conducting PMCA reactions in the presence of Teflon beads (PMCAb) increased the conversion of PrPC into PrPSc from ∼10% to up to 100%. In PMCAb, a single 24-hour round consistently amplified PrPSc by 600-700-fold. Furthermore, the sensitivity of prion detection in one round (24 hours) increased by 2-3 orders of magnitude. Using serial PMCAb, a 1012-fold dilution of scrapie brain material could be amplified to the level detectible by Western blotting in 3 rounds (72 hours). The improvements in amplification efficiency were observed for the commonly used hamster 263K strain and for the synthetic strain SSLOW that otherwise amplifies poorly in PMCA. The increase in the amplification efficiency did not come at the expense of prion replication specificity. The current study demonstrates that poor conversion efficiencies observed previously have not been due to the scarcity of a sub-fraction of PrPC susceptible to conversion nor due to limited concentrations of essential cellular cofactors required for conversion. The new PMCAb format offers immediate practical benefits and opens new avenues for developing fast ultrasensitive assays and for producing abundant quantities of PrPSc in vitro.

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“…A red cell filter device, P-Capt (Macopharma, Tourcoing, France), incorporating a specific resin designed to remove prions (Gregori et al, 2006), the infectious agent in blood thought to cause vCJD, was CE marked in Europe in 2006. P-Capt filtered red blood cell concentrates (PF-RCC) behaved normally in laboratory assays and had a normal antigenic profile (Murphy et al, 2009), and a study in 20 patients showed that exposure to 1-2 PF-RCC units did not generate any attributable adverse events (Cahill et al, 2010).…”

mentioning

confidence: 99%

Transfusion of prion‐filtered red cells does not increase the rate of alloimmunization or transfusion reactions in patients: results of the UK trial of prion‐filtered versus standard red cells in surgical patients (PRISM A)

et al. 2013

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SummaryThis study, conducted for the UK Blood Transfusion Services (UKBTS), evaluated the clinical safety of red cells filtered through a CE-marked prion removal filter (P-Capt). Patients requiring blood transfusion for elective procedures in nine UK hospitals were entered into a non-randomized open trial to assess development of red cell antibodies to standard red cell (RCC) or prion-filtered red cell concentrates (PF-RCC) at eight weeks and six months post-transfusion. Patients who received at least 1 unit of PF-RCC were compared with a control cohort given RCC only. About 917 PF-RCC and 1336 RCC units were transfused into 299 and 291 patients respectively. Twenty-six new red cell antibodies were detected post-transfusion in 10 patients in each arm, an overall alloimmunization rate of 4Á4%. Neither the treatment arm [odds ratio (OR) 0Á93, 95% confidence interval (CI) 0Á3, 2Á5] nor number of units transfused (OR 0Á95, 95% CI 0Á8, 1Á1) had a significant effect on the proportion of patients who developed new alloantibodies. No pan-reactive antibodies or antibodies specifically against PF-RCC were detected. There was no difference in transfusion reactions between arms, and no novel transfusion-related adverse events clearly attributable to PF-RCC were seen. These data suggest that prion filtration of red cells does not reduce overall transfusion safety. This finding requires confirmation in large populations of transfused patients.

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Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands

Cited by 63 publications

References 9 publications

Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster

Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster

Highly Efficient Protein Misfolding Cyclic Amplification

Transfusion of prion‐filtered red cells does not increase the rate of alloimmunization or transfusion reactions in patients: results of the UK trial of prion‐filtered versus standard red cells in surgical patients (PRISM A)

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