Research ArticlePrion Disease

Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease

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Science Translational Medicine  22 Nov 2017:
Vol. 9, Issue 417, eaam7785
DOI: 10.1126/scitranslmed.aam7785

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Prions in unexpected places

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, can be transmitted via neurosurgical instruments or corneal or dura mater transplants contaminated by infectious prions. Some epidemiological studies have associated sCJD risk with surgeries that involve the skin, but whether the skin of sCJD patients contains prion infectivity is not known. Orrú et al. now report detectable prion seeding activity and infectivity in skin from sCJD patients, although at much lower levels compared to brain tissues from sCJD patients. These data suggest that there may be a potential for iatrogenic sCJD transmission through skin.

Abstract

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible through iatrogenic routes due to abundant infectious prions [misfolded forms of the prion protein (PrPSc)] in the central nervous system (CNS). Some epidemiological studies have associated sCJD risk with non-CNS surgeries. We explored the potential prion seeding activity and infectivity of skin from sCJD patients. Autopsy or biopsy skin samples from 38 patients [21 sCJD, 2 variant CJD (vCJD), and 15 non-CJD] were analyzed by Western blotting and real-time quaking-induced conversion (RT-QuIC) for PrPSc. Skin samples from two patients were further examined for prion infectivity by bioassay using two lines of humanized transgenic mice. Western blotting revealed dermal PrPSc in one of five deceased sCJD patients and one of two vCJD patients. However, the more sensitive RT-QuIC assay detected prion seeding activity in skin from all 23 CJD decedents but not in skin from any non-CJD control individuals (with other neurological conditions or other diseases) during blinded testing. Although sCJD patient skin contained ~103- to 105-fold lower prion seeding activity than did sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated with sCJD skin homogenates from two sCJD patients succumbed to prion disease within 564 days after inoculation. Our study demonstrates that the skin of sCJD patients contains both prion seeding activity and infectivity, which raises concerns about the potential for iatrogenic sCJD transmission via skin.

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