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 asymptomatic variant Creutzfeldt-Jakob disease (CJD) patients implicate the presence of prion infectivity in peripheral blood. In this study, we examined the levels of the normal, cellular prion protein (PrP(C)) and the disease-causing isoform (PrP(Sc)) in subpopulations of circulating white blood cells (WBC) from sporadic (s) CJD patients, age-matched neurological controls and healthy donors. Though widely distributed, the highest levels of PrP(C) were found in a subpopulation of T lymphocytes: ~12,000 PrP(C) molecules were found per CD4(+)CD45RA(-)CD62L(-) effector memory T helper cell. While platelets expressed low levels of PrP(C) on their surface, their high abundance in circulation resulted in the majority of PrP(C) being platelet associated. Using quantitative FACS analysis, we found that neither WBC composition nor the amount of cell-surface PrP(C) molecules was altered in patients dying of sCJD. Eight different WBC fraction types from the peripheral blood of sCJD patients were assessed for PrP(Sc). We were unable to find any evidence for PrP(Sc) in purified granulocytes, monocytes, B cells, CD4(+) T cells, CD8(+) T cells, NK cells, non-classical γδT cells, or platelets. If human WBCs harbor prion infectivity in sCJD patients, then the levels are likely to be low.