Impacts and concerns for vCJD in blood transfusion: current status.
The impact of vCJD upon blood transfusion practice hinges on its lymphoreticular involvement. B lymphocytes play a key supporting role for the capture and replication of infectivity by follicular dendritic cells of the lymphoid tissue in animal models of transmissible spongiform encephalopathies (TSE) and tonsils, spleen and appendix in man can harbour vCJD infectivity, a situation not seen with the other human TSEs. Leucodepletion of blood donations in the UK was implemented to reduce possible vCJD transmission and preliminary data suggests that white cell associated infectivity will be effectively removed although plasma infectivity will not. Blood screening assays are under development but none yet are ready for application. The conformation dependant immunoassay, based on differences in secondary and tertiary structure between normal and TSE-associated abnormal prion protein, has a sensitivity now approaching the best bioassay. Even so further development is needed to detect the fg/ml levels likely in the event that vCJD blood does contain abnormal prion, which is as yet unproven. Surrogate assays, such as for erythroid associated factor, may provide additional means of identifying donors harbouring vCJD. Validation of clearance of TSEs from pooled plasma products consistently demonstrates effective removal of the agents in downscaled systems and studies comparing vCJD, BSE and scrapie agents yield similar results. Many approaches to therapy are under investigation, in cell culture and animal models, targeted to normal or abnormal prion metabolism, including chemical and immunological interventions. Efficacy of quinacrine/chlorpromazine and pentosan polysulphate in a clinical setting, and agents yet to be used, will be more accurately known following recent agreement of clinical drug evaluation protocols.
MacGregor
I R
IR
Products and Components R&D Group, National Science Laboratory, Scottish National Blood Transfusion Service, Edinburgh EH17 7QT, UK. ian.macgregor@snbts.csa.scot.nhs.uk
Prowse
C V
CV
D000818:Animals; D015415:Biomarkers; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood / Q000628:therapy / Q000635:transmission*; D006224:Cricetinae; D004195:Disease Models, Animal; D007118:Immunoassay; D008403:Mass Screening; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000097:blood / Q000635:transmission; D012756:Sheep; D065227:Transfusion Reaction
D015415:Biomarkers