Age-related expression of the cellular prion protein in human peripheral blood leukocytes

Background and Objectives. Creutzfeldt-Jakob disease typically affects olde r patients, yet victims of new-variant Creutzfeldt-Jakob disease (nvCJD) ar e usually young. Because the cellular prion protein is required for disease development, we investigated age-dependent variability in cell surface exp ression on various subclasses of human peripheral blood leukocytes (PBL) as a possible susceptibility factor. Design and Methods. Three age groups of healthy Individuals (mean ages: 6, 33 and 68) were studied by two-color FAGS analysis of PBL with fluorescent monoclonal antibodies to PrPC and to the lineage markers CD3, CD19, CD4, an d CD8. For each subclass marker, surface PrPC levels were expressed as mean fluorescence intensity ratios (MFIR) by dividing the geometric mean of the fluorescence of each test antibody by the geometric mean of its Isotype-ma tched control antibody. PrPC expression levels in each age and lineage grou p were compared using appropriate non-parametric tests. Results. We found significant age-related differences In PrPC expression on lymphocytes (p=0.0004), The elderly expressed significantly higher levels than children (p=0.0006) and adults (p=0.0009), PrPC expression was also si gnificantly higher in CD3(+) compared to CD19(+)(p=0.0004) and in CD8(+) co mpared to CD4(+) lymphocytes( p=0.0044). Interpretation and Conclusions. If PrPC expression on PBL were a significan t susceptibility factor for nvCJD, young persons would display higher level s. Instead the elderly expressed the highest amounts of PrPC on PBL, This a rgues against the hypothesis variability in cell surface expression of PrPC in contributes to the exquisite susceptibility of the young to nvCJD, (C) 2000, Ferrata Storti Foundation.