Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

PLoS Pathogens

Jean-Marc Bilheude¹  Mark W. Head²  Stéphanie Simon³  Jean-Jacques Hauw³  Armand Perret-Liaudet⁴  Jan Langeveld⁴  Caroline Lacroux⁵  Olivier Andréoletti⁵  Emmanuelle Uro-Coste⁵  Stéphane Haik⁶  James W. Ironside⁷  Jacques Grassi⁷  Christelle Basset-Leobon⁸  Francois Schelcher⁸  Nathalie Streichenberger⁹  Marie Bernadette Delisle^1,10  Katell Peoch'^1,10  Séverine Lugan^1,10  Hervé Cassard^1,10 

[1] Bio-Rad, Research and Development Department, Marnes-la-Coquette, France;Central Institute for Animal Disease Control CIDC-Lelystad, Lelystad, The Netherlands;Commissariat à l'Energie Atomique (CEA), Service de Pharmacologie et d'Immunologie, DRM, CEA/Saclay, Gif sur Yvette, France;Hôpital Neurologique, Services de Neurochimie et de Pathologie, Bron, France;INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France;INSERM, Equipe Avenir, Maladies à Prions chez l'Homme, Paris, France;National Creutzfeldt-Jakob Disease Surveillance Unit, Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom;Neuropathology Laboratory, Salpêtrière Hospital, AP-HP, Paris, France;Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, Paris (Laboratoire associé au CNR “ATNC”) et EA 3621 Faculté de Pharmacie, Paris, France;UMR Institut National de la Recherche Agronomique (INRA)/Ecole Nationale Vétérinaire de Toulouse (ENVT) 1225, Interactions Hôtes Agents Pathogènes, ENVT, Toulouse, France

关键词: Creutzfeldt-Jakob disease;    Enzyme-linked immunoassays;    Prion diseases;    Detergents;    Protein sequencing;    Frontal lobe;    Molecular strains;    Cerebellum;   

DOI  :  10.1371/journal.ppat.1000029

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability.

【 授权许可】

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