Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: An inter-rater study among surveillance centres in Europe and USA

Piero Parchi, Laura De Boni, Daniela Saverioni, Mark L. Cohen, Isidro Ferrer, Pierluigi Gambetti, Ellen Gelpi, Giorgio Giaccone, Jean Jacques Hauw, Romana Höftberger, James W. Ironside, Casper Jansen, Gabor G. Kovacs, Annemieke Rozemuller, Danielle Seilhean, Fabrizio Tagliavini, Armin Giese, Hans A. Kretzschmar

Research output: Contribution to journalArticle

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Abstract

The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the proteaseresistant core of the abnormal prion protein, PrP Sc (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrPSc typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrPSc types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt-Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrPSc typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy.

Original languageEnglish
Pages (from-to)517-529
Number of pages13
JournalActa Neuropathologica
Volume124
Issue number4
DOIs
Publication statusPublished - Oct 2012

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Prion Diseases
Consensus
Creutzfeldt-Jakob Syndrome
Phenotype
Molecular Typing
Valine
Codon
Methionine
Western Blotting
Genotype

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Cite this

Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes : An inter-rater study among surveillance centres in Europe and USA. / Parchi, Piero; De Boni, Laura; Saverioni, Daniela; Cohen, Mark L.; Ferrer, Isidro; Gambetti, Pierluigi; Gelpi, Ellen; Giaccone, Giorgio; Hauw, Jean Jacques; Höftberger, Romana; Ironside, James W.; Jansen, Casper; Kovacs, Gabor G.; Rozemuller, Annemieke; Seilhean, Danielle; Tagliavini, Fabrizio; Giese, Armin; Kretzschmar, Hans A.

In: Acta Neuropathologica, Vol. 124, No. 4, 10.2012, p. 517-529.

Research output: Contribution to journalArticle

Parchi, P, De Boni, L, Saverioni, D, Cohen, ML, Ferrer, I, Gambetti, P, Gelpi, E, Giaccone, G, Hauw, JJ, Höftberger, R, Ironside, JW, Jansen, C, Kovacs, GG, Rozemuller, A, Seilhean, D, Tagliavini, F, Giese, A & Kretzschmar, HA 2012, 'Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: An inter-rater study among surveillance centres in Europe and USA', Acta Neuropathologica, vol. 124, no. 4, pp. 517-529. https://doi.org/10.1007/s00401-012-1002-8
Parchi, Piero ; De Boni, Laura ; Saverioni, Daniela ; Cohen, Mark L. ; Ferrer, Isidro ; Gambetti, Pierluigi ; Gelpi, Ellen ; Giaccone, Giorgio ; Hauw, Jean Jacques ; Höftberger, Romana ; Ironside, James W. ; Jansen, Casper ; Kovacs, Gabor G. ; Rozemuller, Annemieke ; Seilhean, Danielle ; Tagliavini, Fabrizio ; Giese, Armin ; Kretzschmar, Hans A. / Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes : An inter-rater study among surveillance centres in Europe and USA. In: Acta Neuropathologica. 2012 ; Vol. 124, No. 4. pp. 517-529.
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AU - Hauw, Jean Jacques

AU - Höftberger, Romana

AU - Ironside, James W.

AU - Jansen, Casper

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