JC is a Director and JC and JDFW are shareholders and consultants of D-Gen Limited, an academic spin-out company working in the field of prion disease diagnosis, decontamination, and therapeutics. D-Gen markets the ICSM35 antibody used in this study. SB carries out a large-scale screening study for the detection of abnormal prion protein in archival appendix samples. This study was commissioned in a competitive tender by the UK Health Protection Agency. The other authors declare no conflicts of interest.
Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study†
Article first published online: 10 DEC 2010
Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 223, Issue 4, pages 511–518, March 2011
How to Cite
Wadsworth, J. D., Dalmau-Mena, I., Joiner, S., Linehan, J. M., O'Malley, C., Powell, C., Brandner, S., Asante, E. A., Ironside, J. W., Hilton, D. A. and Collinge, J. (2011), Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study. J. Pathol., 223: 511–518. doi: 10.1002/path.2821
- Issue published online: 3 FEB 2011
- Article first published online: 10 DEC 2010
- Accepted manuscript online: 11 NOV 2010 07:18AM EST
- Manuscript Accepted: 6 NOV 2010
- Manuscript Revised: 21 OCT 2010
- Manuscript Received: 14 SEP 2010
- Medical Research Council
- Re-use of this article is permitted in accordance with the Terms and Conditions set out at . [http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms]
- variant Creutzfeldt–Jakob disease;
- prion disease;
- prion strain;
- prion transmission;
- bovine spongiform encephalopathy
Anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the UK population prevalence of asymptomatic vCJD prion infection. The retrospective study of Hilton et al(J Pathol 2004; 203: 733–739) found accumulation of abnormal prion protein in three formalin-fixed appendix specimens. This led to an estimated UK prevalence of vCJD infection of ∼1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic transmission of vCJD prions in the UK. Confirmatory testing of these positives has been hampered by the inability to perform immunoblotting of formalin-fixed tissue. Animal transmission studies offer the potential for ‘gold standard’ confirmatory testing but are limited by both transmission barrier effects and known effects of fixation on scrapie prion titre in experimental models. Here we report the effects of fixation on brain and lymphoreticular human vCJD prions and comparative bioassay of two of the three prevalence study formalin-fixed, paraffin-embedded (FFPE) appendix specimens using transgenic mice expressing human prion protein (PrP). While transgenic mice expressing human PrP 129M readily reported vCJD prion infection after inoculation with frozen vCJD brain or appendix, and also FFPE vCJD brain, no infectivity was detected in FFPE vCJD spleen. No prion transmission was observed from either of the FFPE appendix specimens. The absence of detectable infectivity in fixed, known positive vCJD lymphoreticular tissue precludes interpreting negative transmissions from vCJD prevalence study appendix specimens. In this context, the Hilton et al study should continue to inform risk assessment pending the outcome of larger-scale studies on discarded surgical tissues and autopsy samples. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.