BACKGROUND: The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrP(Sc)), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrP(Sc) display unglycosylated core fragments of 21 kDa and 19 kDa, resulting from cleavage around amino acids 82 and 97, respectively. METHODS: We generated anti-PrP monoclonal antibodies to epitopes immediately preceding the differential proteinase K cleavage sites. These antibodies, which were designated POM2 and POM12, recognise type 1, but not type 2, PrP(Sc). FINDINGS: We studied 114 brain samples from 70 patients with sporadic CJD and three patients with variant CJD. Every patient classified as CJD type 2, and all variant CJD patients, showed POM2/POM12 reactivity in the cerebellum and other PrP(Sc)-rich brain areas, with a typical PrP(Sc) type 1 migration pattern. INTERPRETATION: The regular coexistence of multiple PrP(Sc) types in patients with CJD casts doubts on the validity of electrophoretic PrP(Sc) mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.
BACKGROUND: The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrP(Sc)), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrP(Sc) display unglycosylated core fragments of 21 kDa and 19 kDa, resulting from cleavage around amino acids 82 and 97, respectively. METHODS: We generated anti-PrP monoclonal antibodies to epitopes immediately preceding the differential proteinase K cleavage sites. These antibodies, which were designated POM2 and POM12, recognise type 1, but not type 2, PrP(Sc). FINDINGS: We studied 114 brain samples from 70 patients with sporadic CJD and three patients with variant CJD. Every patient classified as CJD type 2, and all variant CJDpatients, showed POM2/POM12 reactivity in the cerebellum and other PrP(Sc)-rich brain areas, with a typical PrP(Sc) type 1 migration pattern. INTERPRETATION: The regular coexistence of multiple PrP(Sc) types in patients with CJD casts doubts on the validity of electrophoretic PrP(Sc) mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.
Authors: Juan Carlos Espinosa; Olivier Andréoletti; Joaquín Castilla; María Eugenia Herva; Mónica Morales; Elia Alamillo; Fayna Díaz San-Segundo; Caroline Lacroux; Séverine Lugan; Francisco Javier Salguero; Jan Langeveld; Juan María Torres Journal: J Virol Date: 2006-11-01 Impact factor: 5.103
Authors: Jason C Bartz; Michelle L Kramer; Meghan H Sheehan; Jessica A L Hutter; Jacob I Ayers; Richard A Bessen; Anthony E Kincaid Journal: J Virol Date: 2006-11-01 Impact factor: 5.103
Authors: Mark Zabel; Christina Greenwood; Alana M Thackray; Bruce Pulford; Willem Rens; Raymond Bujdoso Journal: Immunology Date: 2008-10-21 Impact factor: 7.397
Authors: Alba Marín-Moreno; Patricia Aguilar-Calvo; José Luis Pitarch; Juan Carlos Espinosa; Juan María Torres Journal: J Virol Date: 2018-11-27 Impact factor: 5.103