Prion proteins in subpopulations of white blood cells from patients with sporadic Creutzfeldt-Jakob disease

Recent cases of prion transmission in humans following transfusions using blood donated by patients with asymptomatic variant Creutzfeldt-Jakob disease (CJD) implicate the presence of prion infectivity in peripheral blood. In this study, we examined the levels of the normal, cellular prion protein (PrPC), and the disease-causing isoform (PrPSc) in subpopulations of circulating white blood cells (WBCs) from patients with sporadic (s) CJD, age-matched neurological controls and healthy donors. Though widely distributed, the highest levels of PrPC were found in a subpopulation of T lymphocytes: similar to 12 000 PrPC molecules were found per CD4(+)CD45RA(-)CD62L(-) effector memory T helper cell. Although platelets expressed low levels of PrPC on their surface, their high abundance in circulation resulted in the majority of PrPC being platelet associated. Using quantitative fluorescence-activated cell sorting analysis, we found that neither WBC composition nor the amount of cell-surface PrPC molecules was altered in patients with sCJD. Eight different WBC fraction types from the peripheral blood of patients with sCJD were assessed for PrPSc. We were unable to find any evidence for PrPSc in purified granulocytes, monocytes, B cells, CD4(+) T cells, CD8(+) T cells, natural killer cells, nonclassical gamma delta T cells, or platelets. If human WBCs harbor prion infectivity in patients with sCJD, then the levels are likely to be low. Laboratory Investigation (2009) 89, 624-635; doi:10.1038/labinvest.2009.30; published online 11 May 2009