title: Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease.
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.
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France. joliette.coste@efs.sante.fr daisy.bougard@efs.sante.fr.
authors.forename: Daisy
authors.initials: D
authors.lastname: Bougard
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut du Cerveau et de la Moelle épinière (ICM)-Hôpital Pitié-Salpêtrière, F-75013 Paris, France.|Assistance publique-Hôpitaux de Paris, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.|Centre National de Référence des Agents Transmissibles Non Conventionnels, F-75013 Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Brandel
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Bélondrade
authors.affiliation: Institut National de la Recherche Agronomique, Université Paris-Saclay, Virologie Immunologie Moléculaire, F-78350 Jouy-en-Josas, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Segarra
authors.affiliation: Laboratoire de Virologie, Hôpital Pellegrin, F-33076 Bordeaux, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
authors.affiliation: Centre National de Référence des Agents Transmissibles Non Conventionnels, F-75013 Paris, France.|Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, F-75010 Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France.
authors.forename: Charly
authors.initials: C
authors.lastname: Mayran
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Nicot
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, U.K.
authors.forename: Alison
authors.initials: A
authors.lastname: Green
authors.affiliation: Assistance publique-Hôpitaux de Paris, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Welaratne
authors.affiliation: Etablissement Français du Sang, F-93218 La Plaine Saint Denis, France.
authors.forename: David
authors.initials: D
authors.lastname: Narbey
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Fournier-Wirth
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, U.K.
authors.forename: Richard
authors.initials: R
authors.lastname: Knight
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, U.K.
authors.forename: Robert
authors.initials: R
authors.lastname: Will
authors.affiliation: Etablissement Français du Sang, F-93218 La Plaine Saint Denis, France.|INSERM, Etablissement Français du Sang, Université de Franche-Comté, UMR 1098, F-25020 Besançon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiberghien
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut du Cerveau et de la Moelle épinière (ICM)-Hôpital Pitié-Salpêtrière, F-75013 Paris, France.|Assistance publique-Hôpitaux de Paris, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.|Centre National de Référence des Agents Transmissibles Non Conventionnels, F-75013 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Haïk
authors.affiliation: Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France. joliette.coste@efs.sante.fr daisy.bougard@efs.sante.fr.|Etablissement Français du Sang, F-93218 La Plaine Saint Denis, France.
authors.forename: Joliette
authors.initials: J
authors.lastname: Coste
mesh_terms: D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood* / Q000175:diagnosis*; D005602:France; D006403:Hematologic Tests / Q000379:methods*; D006801:Humans; D000072002:Prion Proteins / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000072002:Prion Proteins