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The letter by Joiner et al1 describes the lack of detectable prion protein (PrP) in three of four necropsy appendix samples from vCJD cases using a combination of immunocytochemistry and western blotting, thereby questioning the value of large scale screening of appendix tissue samples as an estimate of people who may be incubating vCJD. In our original description of PrP accumulation in the appendix before the onset of symptoms2 we noted that PrP accumulation was focal and therefore we have used extensive sampling of the appendix for our study, resulting in a median of more than 24 secondary lymphoid follicles examined in each appendix case included. In addition we have used two different monoclonal antibodies to PrP and a very sensitive detection system,3 to reduce the risk of false negatives. Using this approach we were able to detect lymphoreticular PrP accumulation in 19 of 22 vCJD necropsy appendix samples tested (two of the three negative samples had inadequate amounts of lymphoid tissue for assessment and would not have met inclusion criteria for our study3). In addition, of the three appendix samples removed before the onset of symptoms, the two removed in the 1990s were positive, and the third, removed in 1987 was negative.3 All samples included in our study were removed between 1995 and 1999. The discrepancy between our findings and those of Joiner et al1 may therefore result from our use of a more sensitive immunocytochemical approach and extensive tissue sampling.
While we accept that the sensitivity and specificity of screening tissue samples for lymphoreticular accumulation of PrP as a marker for vCJD is unknown, it seems to be a reliable approach in animals,4 and given the lack of an alternative test and considerable uncertainty about future numbers of vCJD cases, we feel that such a study is justified. Our study has necessarily concentrated on appendix samples (as comparatively few tonsillectomy samples are archived), however we have recommended large scale screening of fresh tonsil tissue on a prospective basis,3 which the Department of Health has now agreed to undertake.
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