High levels of disease related prion protein in the ileum in variant Creutzfeldt-Jakob disease

Abstract

Tissues were obtained at autopsy with consent from relatives from four patients with neuropathologically confirmed vCJD and two patients with neuropathologically confirmed sporadic CJD (both PRNP codon 129MM with type 2 PrP^Sc in brain). Terminal ileum was analysed for PrP^Sc by high sensitivity immunoblotting³ and for abnormal PrP immunoreactivity by immunohistochemistry.⁶ Using these methods, terminal ileum from all four vCJD cases showed high levels of detectable PrP^Sc (fig 1A). In three vCJD cases, 2/2 homogenates prepared from each ileum specimen were positive for PrP^Sc whereas 2/4 ileum homogenates were positive in the other vCJD case. The glycoform ratio of protease resistant fragments of di-, mono-, and non-glycosylated PrP in terminal ileum appeared to be closely similar to the type 4t PrP^Sc pattern seen in vCJD tonsil.^{2, 3} Although there was variation in PrP^Sc concentration between different homogenates of vCJD terminal ileum, PrP^Sc levels in positive samples were typically in the range 0.1–1% of that present in vCJD brain (fig 1B). With respect to both sampling variation and PrP^Sc concentration, terminal ileum appears to be closely similar to lymph nodes in vCJD.³ These findings, together with our previous studies, show that PrP^Sc deposition within the intestine is not uniform in vCJD. From the four cases of vCJD with PrP^Sc positive terminal ileum studied here, 0/2 cases with available tissue had detectable PrP^Sc in the appendix^{3, 10} and only 1/3 cases had detectable PrP^Sc in the rectum.³ In contrast with findings with vCJD terminal ileum, no detectable PrP^Sc was found in homogenates of terminal ileum prepared from sporadic CJD patients (fig 1A). The lack of detection of PrP^Sc in sporadic CJD terminal ileum extends our previous findings for one of these cases in which we have previously reported a lack of detectable PrP^Sc in tonsil, rectum, and appendix.^{3, 10}