Irregular presence of abnormal prion protein in appendix in variant Creutzfeldt-Jakob disease.

We have investigated the presence of disease related prion protein (PrP) in appendix samples obtained at necropsy from four neuropathologically confirmed cases of variant Creutzfeldt-Jakob disease (vCJD). PrP was detected in only one vCJD appendix, at a level lower than found in a diagnostic tonsil biopsy sample obtained from the same patient. The single PrP positive appendix, but not the other samples, also showed abnormal prion protein immunohistochemistry. The finding that appendix samples from three of four cases of vCJD are devoid of detectable PrP questions the utility of screening archival appendicectomy tissues to estimate the prevalence of pre-clinical vCJD infection within the UK population. The appearance of a novel human prion disease, variant Creutzfeldt-Jakob disease (vCJD), in the United Kingdom from 1995 onwards, and the experimental confirmation that this is caused by the same prion strain as that causing BSE in cattle, has raised the possibility that a major epidemic of vCJD will occur in the United Kingdom and other countries as a result of dietary or other exposure to BSE prions. The pathogenesis of vCJD differs significantly from that of other forms of CJD. Disease associated prion protein (PrP) is readily detectable in lymphoreticular tissues in vCJD and not in classic CJD. High levels of PrP are uniformly found in the central nervous system and lymphoreticular system of vCJD patients. 3 The highest levels of PrP seen outside the central nervous system in vCJD are in tonsil (about 10% of that found in brain) 3 and tonsil biopsy is used for antemortem diagnosis of vCJD. To date, positive prion protein immunohistochemistry has been reported in only a single appendix sample, although, importantly, this was removed from the patient before the onset of overt features of vCJD. While the stage at which lymphoreticular infection occurs in vCJD is unknown, PrP accumulation is detectable in the lymphoreticular system in natural sheep scrapie and in experimental rodent models of scrapie at a very early stage of the incubation period, long before the clinical phase of the disease. Based upon these data it has been suggested that large scale screening of surgical tonsillectomy and appendicectomy tissues for PrP could provide early warning of a high level of vCJD prion infection and several such studies are in progress. 5 Recently we reported our concern after finding that PrP was undetectable in appendix samples obtained at necropsy from two neuropathologically confirmed vCJD cases. While we were not able to examine these samples using immunohistochemical methods, we have now had the opportunity to investigate appendixes from two further vCJD cases by both high sensitivity western blotting and immunohistochemistry.