Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay

Factors intrinsic and extrinsic to blood hamper the development of a routine blood test for human prion diseases

“…In another assay, instead of concentrating PrP TSE by IP with anti-PrP antibodies, PrP TSE was concentrated from human whole blood by capturing it on stainless steel beads before immunodetection using a solid-state capture matrix-ELISA (Edgeworth et al, 2011). This assay was shown to be more efficient than IP with antibodies, and allowed the detection of PrP TSE in human whole blood spiked with high dilutions (up to 10 210 ) of vCJD-infected brain homogenate, and in the whole blood of 15 of 21 symptomatic patients with vCJD H. Abdel-Haq with 71.4 % sensitivity and 100 % specificity.…”

“…Some of the assays reviewed here, particularly the solidstate matrix assays (Lourenco et al, 2006;Edgeworth et al, 2011;Lacroux et al, 2014), demonstrated that it is possible to detect PrP TSE in the blood of symptomatic vCJD patients. This is a marked advance in the diagnosis of prion diseases, indicating that a blood test is possible, although not yet suitable, for routine use.…”

“…These tests displayed low sensitivity, which appears to be the main obstacle to their routine employment. However, based on the fact that PrP TSE from vCJD-infected brain homogenate spiked into whole blood can be detected with good sensitivity at dilution of 10 210 , hypothetically, it should be possible to detect prions in the blood of vCJD patients at the preclinical stage of the disease (Edgeworth et al, 2011). Moreover, given that other blood tests based on different principles showed similar behaviour, but that not all blood samples obtained from clinically affected subjects tested positive for PrP TSE (Terry et al, 2009;Bannach et al, 2012;Jackson et al, 2014;Lacroux et al, 2014), the sensitivity of the tests is unlikely to be the only factor responsible for the failed detection of PrP TSE .…”

First Demonstration of Transmissible Spongiform Encephalopathy-associated Prion Protein (PrPTSE) in Extracellular Vesicles from Plasma of Mice Infected with Mouse-adapted Variant Creutzfeldt-Jakob Disease by in Vitro Amplification

“…FVB mice in the experimental groups were euthanized when they developed clinical signs of TSE. C57BL mice were euthanized periodically during the incubation period (6,9,12,15, and 20 weeks post inoculation (wpi)) and at clinical onset (ϳ23 wpi). Negative controls were euthanized at the end of the experiment, together with the last mouse from the experimental group.…”

“…Recently, infectivity was reported in the plasma of two out of four patients affected by sporadic CJD (sCJD) (11). Although similar levels of PrP TSE have been detected in spleens, tonsils, and lymph nodes of vCJD and sCJD patients by Western blotting (12), the identification of this protein in the blood of individuals afflicted with the latter by various methods, including PrP TSE capture coupled to direct immunodetection of surface-bound material (6), capillary electrophoresis (13), and protein misfolding cyclic amplification (PMCA) coupled to surrounding optical fiber immunoassay (12), has been highly elusive for decades, with only two cases recently reported (8). Nevertheless, extensive epidemiological data continue to provide no evidence of human-to-human transmission of sCJD through blood transfusion (14).…”