title: Comparative Study of Prions in Iatrogenic and Sporadic Creutzfeldt-Jakob Disease.
abstract: Differentiating iatrogenic Creutzfeldt-Jakob disease (iCJD) from sporadic CJD (sCJD) would be useful for the identification and prevention of human-to-human prion transmission. Currently, the diagnosis of iCJD depends on identification of a recognized source of contamination to which patients have been exposed, in addition to fulfilling basic requirements for the establishment of diagnosis of CJD. Attempts to identify differences in clinical manifestations, neuropathological changes and pathological prion protein (PrPSc) between iCJD and sCJD have been unsuccessful. In the present study, using a variety of more sophisticated methods including sucrose step gradient sedimentation, conformational stability immunoassay, protein misfolding cyclic amplification (PMCA), fragment-mapping, and transmission study, we show no significant differences in gel profiles, oligomeric state, conformational stability and infectivity of PrPScbetween iCJD and sCJD. However, using PMCA, we find that convertibility and amplification efficiency of PrPScis greater in iCJD than in sCJD in a polymorphism-dependent manner. Moreover, two protease-resistant PrP C-terminal fragments (termed PrP-CTF12/13) were detected in all 9 cases of sCJD but not in 6 of 8 cases of iCJD tested in this study. The use of fragment mapping- and PMCA-based assays thus provides a means to distinguish most cases of iCJD from sCJD.
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Liuting
authors.initials: L
authors.lastname: Qing
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA ; Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.affiliation: Department of Pathology, Hôpital Lariboisière, 2 rue Ambroise Paré, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mikol
authors.affiliation: Department of Pathology, Rangueil University Hospital, avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France ; INSERM U858, I2MR, Team 15, BP 84225, 31432 Toulouse Cedex 4, France.
authors.forename: Marie-Bernadette
authors.initials: MB
authors.lastname: Delisle
authors.affiliation: Department of Pathology, Rangueil University Hospital, avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France ; INSERM U858, I2MR, Team 15, BP 84225, 31432 Toulouse Cedex 4, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Uro-Coste
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA ; The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Mai
authors.initials: M
authors.lastname: Abouelsaad
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Gazgalis
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Manuel Camacho
authors.initials: MC
authors.lastname: Martinez
authors.affiliation: The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Gong-Xian
authors.initials: GX
authors.lastname: Wang
authors.affiliation: Laboratoire Français des Biotechnologies (LFB), Les Ulis, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brown
authors.affiliation: National Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital Edinburgh, EH4 2XU, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA ; Department of Neurology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Pathology and National Prion Disease, Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA ; Department of Neurology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA ; National Center for Regenerative Medicine, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA ; The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
keywords: Human prion diseases; Iatrogenic Creutzfeldt-Jakob disease; Sporadic CJD