Ritchie, DL;
Barria, MA;
Peden, AH;
Yull, HM;
Kirkpatrick, J;
Adlard, P;
Ironside, JW;
(2017)
UK Iatrogenic Creutzfeldt-Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches.
Acta Neuropathol
, 133
(4)
pp. 579-595.
10.1007/s00401-016-1638-x.
Preview |
Text
Adlard_10.1007_s00401-016-1638-x.pdf - Published Version Download (3MB) | Preview |
Abstract
Creutzfeldt-Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show the interplay of prion strain and host genotype in governing the molecular, pathological and temporal characteristics of the UK hGH-iCJD epidemic and provide insights into the adaptive mechanisms involved when prions cross genotypic barriers. We conclude that all of the available evidence is consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is associated with the second most common form of sporadic CJD.
| Type: | Article |
|---|---|
| Title: | UK Iatrogenic Creutzfeldt-Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches. |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00401-016-1638-x |
| Publisher version: | http://dx.doi.org/10.1007/s00401-016-1638-x |
| Language: | English |
| Additional information: | © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Agent strain, Creutzfeldt–Jakob disease, Disease phenotype, Growth hormone, Iatrogenic, Prion |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1529093 |
Archive Staff Only
 |
View Item |
