The accumulation of PrP(Sc), an abnormal and disease-associated form of the normal
prion protein (PrP(c)), within the central nervous system (CNS) is a key pathological feature of
Creutzfeldt-Jakob disease (CJD). Following limited proteolytic digestion of PrP(Sc), the detection of
PrP(res) within lymphoid tissues is a unique characteristic of variant CJD in comparison with other human
prion diseases, raising fears of an increased risk of iatrogenic spread. Because levels of
PrP(res) in lymphoid tissues are lower than those found in CNS tissue, there is concern that other peripheral tissues may harbour infectivity at levels that current detection systems cannot demonstrate
PrP(res). We have modified the
paraffin-embedded tissue blot (PET blot), a technique combining immunohistochemistry (IHC), histoblot and Western blotting, for the detection of
PrP(res) in
paraffin sections in peripheral tissues in variant CJD. Five cases of variant CJD were examined, using a panel of anti-PrP
antibodies. In each of these five cases, spleen, tonsil, lymph nodes and dorsal root ganglia showed an increase in the sensitivity and specificity of labelling using the PET blot when compared with optimized
PrP(res) IHC methods. Control cases showed no evidence of PrP accumulation in either peripheral or CNS tissues. Autopsy and biopsy brain material from
sporadic CJD cases also showed an increased sensitivity of
PrP(res) detection with the PET blot, confirming its value as an important diagnostic and research tool in human
prion diseases.