In Prion Disease Patients, Prion Seeding Activity in the Digestive System is Similar to Activity in CNS Tissue

Abstract

Background: Human prion diseases (HPD) are neurodegenerative disorders caused by abnormal prion protein, and are associated with the accumulation of abnormal prion protein in the central nervous system. Infectivity had previously been detected only in the central nervous system and lymphoreticular tissues in sporadic Creutzfeldt-Jakob disease (CJD), and peripheral tissue involvement in prion disease, including abnormal prion accumulation in the tonsil, spleen, and lymph node, has been reported in variant CJD and several animal models of prion diseases. Furthermore, recent reports suggest that abnormal prion protein accumulates in various non-neuronal organs including liver, kidney and skin. The aim of this study was to examine abnormal prion accumulation in digestive organs of HPD patients. Methods and Methods: We reanalyzed autopsy samples collected from four sporadic (MM1) and two genetic HPD (E200K and P102L) cases. Analysis of prion seeding activities (PSA) based on real-time quacking-induced conversion assay indicated seeding activity exists in almost all digestive organs. PSA was 109.4-10.18 in brain of all HPD patients, and was 105-7 in digestive organs of all HPD patients. PSA in esophagus was 107.98-8.38 in two of the four sporadic HPD patients and one of the two genetic HPD patients, which was an infectious level similar to that in the central nervous system. Moreover, we identified that PSA was 107-8 in other digestive organs of patients with genetic prion disease. Conclusions: Clinicians should be careful to ensure the safety of endoscopic examinations and operation to prevent accidental transmission of prion protein. Funding: The study was financially supported by grants for scientific research from the Ministry of Health, Labour and Welfare of Japan (KSat: No. 14507303) and Japan Agency for Medical Research and Development (AMED) (grant number No.18ek0109362h0001). Declaration of Interest: All authors should state that none exist in the declarations of interests Ethical Approval: The protocol was approved by the Ethics Committee of Nagasaki University Hospital (ID: 100428423) and was also granted ethical approval for the use of specimens by the Japan CJD Surveillance Unit. The study was registered with the University Hospital Medical Information Network (ID: UMI03301).