Advances in the detection of prion protein in peripheral tissues of variant Creutzfeldt‐Jakob disease patients using paraffin‐embedded tissue blotting

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Abstract
The accumulation of PrPSc, an abnormal and disease‐associated form of the normal prion protein (PrPc), within the central nervous system (CNS) is a key pathological feature of Creutzfeldt‐Jakob disease (CJD). Following limited proteolytic digestion of PrPSc, the detection of PrPres 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 PrPres 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 PrPres. We have modified the paraffin‐embedded tissue blot (PET blot), a technique combining immunohistochemistry (IHC), histoblot and Western blotting, for the detection of PrPres 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 PrPres 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 PrPres detection with the PET blot, confirming its value as an important diagnostic and research tool in human prion diseases.

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