Research ArticlePRION DISEASES

Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease

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Science Translational Medicine  21 Dec 2016:
Vol. 8, Issue 370, pp. 370ra182
DOI: 10.1126/scitranslmed.aag1257

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A new blood test for prion diseases

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease that can be transmitted from person to person through medical procedures. The development of a diagnostic blood test is an urgent priority. Bougard et al. describe a sensitive and specific blood test based on a prion capture step and an amplification method. This test for vCJD was very accurate and worked not only for blood samples from patients suffering from vCJD but also for samples taken from two individuals 1.3 and 2.6 years before they developed clinical symptoms. This blood test has important implications for transfusion medicine and public health.

Abstract

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity [95% confidence interval (CI), 81.5 to 100%], 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion.

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