scholarly journals Validation and Application of Skin RT-QuIC to Patients in China with Probable CJD

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1642
Author(s):  
Kang Xiao ◽  
Xuehua Yang ◽  
Wei Zhou ◽  
Cao Chen ◽  
Qi Shi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Prion Disease ◽  
High Sensitivity ◽  
Definite Diagnosis ◽  
Human Prion Disease ◽  
Positive Skin ◽  
Diagnostic Potential ◽  
Jakob Disease ◽  
The Brain ◽  
Skin Samples

The definite diagnosis of human sporadic Creutzfeldt–Jakob disease (sCJD) largely depends on postmortem neuropathology and PrPSc detection in the brain. The development of real-time quaking-induced conversion (RT-QuIC) of cerebrospinal fluid (CSF) samples makes it possible for premortem diagnosis for sCJD. To test the diagnostic potential of RT-QuIC of skin specimens for probable sCJD, we collected the paired skin and CSF samples from 51 recruited living patients referred to the Chinese CJD surveillance center, including 34 probable sCJD, 14 non-CJD, and 3 genetic prion disease (gPrD). The samples were subjected to RT-QuIC assays using recombinant hamster PrP protein rHaPrP90-231 as the substrate. Using skin RT-QuIC assay, 91.2% (31/34) probable sCJD patients, and 1 T188K genetic CJD (gCJD) cases showed positive prion-seeding activity, while 85.7% (12/14) non-CJD patients were negative. CSF RT-QuIC positive seeding activity was only observed in 14 probable sCJD patients. Analysis of the reactivity of 38 positive skin RT-QuIC tests revealed that the positive rates in the preparations of 10−2, 10−3 and 10−4 diluted skin samples were 88.6% (39/44), 63.6% (28/44), and 25.0% (11/44), respectively. Eleven probable sCJD patients donated two skin specimens collected at different sites simultaneously. Although 95.5% (21/22) skin RT-QuIC elicited positive reaction, the reactivity varied. Our preliminary data indicate high sensitivity and specificity of skin RT-QuIC in prion detection for Chinese probable sCJD and highlight that skin prion-seeding activity is a reliable biomarker for premortem diagnosis of human prion disease.

scholarly journals Skin RT-QuIC Assays are More Sensitive than CSF RT-QuIC in Prion Detection for Chinese Probable Sporadic Creutzfeldt-Jakob Disease

2020 ◽  
Author(s):  
Kang Xiao ◽  
Xue-Hua Yang ◽  
Wei Zhou ◽  
Cao Chen ◽  
Brian S Appleby ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Prion Disease ◽  
Preliminary Data ◽  
High Sensitivity ◽  
Definite Diagnosis ◽  
Human Prion Disease ◽  
Diagnostic Potential ◽  
Jakob Disease ◽  
The Brain ◽  
Skin Specimen

Abstract BackgroundThe definite diagnosis of human sporadic Creutzfeldt-Jakob disease (sCJD) largely depends on postmortem neuropathology and PrPSc detection in the brain. The development of prion RT-QuIC of cerebrospinal fluid (CSF) samples makes it possible for premortem diagnosis for sCJD. However the diagnostic potential of RT-QuIC of skin specimen for probable sCJD is not well researched. This study is to evaluate the diagnostic potential of RT-QuIC of skin specimen in human prion diseases.MethodsWe collected the paired skin and CSF samples from 29 recruited alive patients referred to Chinese CJD surveillance center, including 12 probable sCJD, 9 non-CJD, 3 genetic prion disease (gPrD) and 5 cases whose diagnoses still pending. The samples were subjected to RT-QuIC assays using recombinant hamster PrP protein rHaPrP90-231 as the substrate.ResultsAll 12 probable sCJD patients, 4 pending, and 1 T188K genetic CJD (gCJD) cases showed positive prion-seeding activity, while all 9 non-CJD patients were negative. CSF RT-QuIC positive seeding activity was only observed in 5 probable sCJD patients.ConclusionsOur preliminary data indicate high sensitivity and specificity of skin RT-QuIC in prion detection for Chinese probable sCJD and highlight that skin prion-seeding activity is a reliable biomarker for premortem diagnosis of human prion disease.

Human Prion Diseases

2018 ◽  
pp. 159-171
Author(s):  
James W. Ironside
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Human Prion Disease ◽  
Clinical Genetic ◽  
Jakob Disease ◽  
Biochemical Approach ◽  
Protein Isoform ◽  
The Brain

Human prion diseases include idiopathic, genetic, and acquired disorders. Heterogeneous clinicopathologic features make diagnosis challenging. Accurate diagnosis requires a combined clinical, neuropathologic, genetic, and biochemical approach. Neuropathologic assessment is performed following autopsy in most cases. The brain is sampled and studied by tinctorial stains and immunohistochemistry for disease-associated form of the prion protein. Unfixed frozen brain tissue is retained for Western blot analysis of protease-resistant prion protein isoform and for DNA extraction to sequence the prion protein gene. Assessment of spongiform change, gliosis neuronal loss, and accumulation of disease-associated prion protein in the brain can help to determine major categories of human prion disease. Additional clinical, genetic, and biochemical data allow diagnosis and subclassification into disease subtypes, particularly in sporadic Creutzfeldt–Jakob disease. Neuropathology continues to play a role in the recognition and understanding of the expanding spectrum of human prion disease and identification of disease variants that may emerge in the future.

scholarly journals Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease

2008 ◽  
Vol 363 (1510) ◽  
pp. 3755-3763 ◽  
Author(s):  
Sebastian Brandner ◽  
Jerome Whitfield ◽  
Ken Boone ◽  
Anderson Puwa ◽  
Catherine O'Malley ◽  
...  
Keyword(s):  
Prion Protein ◽  
Human Prion Disease ◽  
Peripheral Tissues ◽  
Prion Strain ◽  
Pathological Analysis ◽  
Lymphoreticular Tissue ◽  
Jakob Disease ◽  
Strain Type ◽  
Few Data ◽  
The Brain

While the neuropathology of kuru is well defined, there are few data concerning the distribution of disease-related prion protein in peripheral tissues. Here we report the investigation of brain and peripheral tissues from a kuru patient who died in 2003. Neuropathological findings were compared with those seen in classical (sporadic and iatrogenic) Creutzfeldt–Jakob disease (CJD) and variant CJD (vCJD). The neuropathological findings of the kuru patient showed all the stereotypical changes that define kuru, with the occurrence of prominent PrP plaques throughout the brain. Lymphoreticular tissue showed no evidence of prion colonization, suggesting that the peripheral pathogenesis of kuru is similar to that seen in classical CJD rather than vCJD. These findings now strongly suggest that the characteristic peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection.

The neuroepidemiology of human prion disease

2020 ◽  
pp. 367-378
Author(s):  
Patrick JM Urwin ◽  
Anna M Molesworth
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Human Prion Disease ◽  
Disease States ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Sporadic Disease

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

scholarly journals Kuru, the First Human Prion Disease

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 232 ◽  
Author(s):  
Paweł Liberski ◽  
Agata Gajos ◽  
Beata Sikorska ◽  
Shirley Lindenbaum
Keyword(s):  
Electron Microscopy ◽  
Confocal Microscopy ◽  
Prion Disease ◽  
Amyloid Plaques ◽  
Human Medicine ◽  
Spongiform Encephalopathy ◽  
Biomedical Sciences ◽  
Human Prion Disease ◽  
History Of ◽  
Jakob Disease

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics. We provide descriptions of electron microscopy and confocal microscopy of kuru amyloid plaques retrieved from a paraffin-embedded block of an old kuru case, named Kupenota. The discovery of kuru opened new vistas of human medicine and was pivotal in the subsequent transmission of Creutzfeldt–Jakob disease, as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century.

Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples

2017 ◽  
Vol 74 (2) ◽  
pp. 155 ◽  
Author(s):  
Matilde Bongianni ◽  
Christina Orrù ◽  
Bradley R. Groveman ◽  
Luca Sacchetto ◽  
Michele Fiorini ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Real Time ◽  
Prion Disease ◽  
Olfactory Mucosa ◽  
Human Prion Disease

Aging, the brain and human prion disease

2002 ◽  
Vol 37 (4) ◽  
pp. 603-605 ◽  
Author(s):  
Gábor G Kovács ◽  
Herbert Budka
Keyword(s):  
Prion Disease ◽  
Human Prion Disease ◽  
The Brain

scholarly journals Wide distribution of prion infectivity in the peripheral tissues of vCJD and sCJD patients

2021 ◽  
Vol 141 (3) ◽  
pp. 383-397
Author(s):  
Jean-Yves Douet ◽  
Alvina Huor ◽  
Hervé Cassard ◽  
Séverine Lugan ◽  
Naima Aron ◽  
...  
Keyword(s):  
Prion Disease ◽  
Wide Distribution ◽  
Human Prion Disease ◽  
Marked Contrast ◽  
Peripheral Tissues ◽  
Spontaneous Formation ◽  
Prion Infectivity ◽  
Clinical Procedures ◽  
Jakob Disease ◽  
The Central Nervous System

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease, occurring most likely as the consequence of spontaneous formation of abnormal prion protein in the central nervous system (CNS). Variant Creutzfeldt–Jakob disease (vCJD) is an acquired prion disease that was first identified in 1996. In marked contrast to vCJD, previous investigations in sCJD revealed either inconsistent levels or an absence of PrPSc in peripheral tissues. These findings contributed to the consensus that risks of transmitting sCJD as a consequence of non-CNS invasive clinical procedures were low. In this study, we systematically measured prion infectivity levels in CNS and peripheral tissues collected from vCJD and sCJD patients. Unexpectedly, prion infectivity was detected in a wide variety of peripheral tissues in sCJD cases. Although the sCJD infectivity levels varied unpredictably in the tissues sampled and between patients, these findings could impact on our perception of the possible transmission risks associated with sCJD.

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