Failure to Demonstrate a Humoral Immune Response to Scrapie Infection in Mice

Porter, David D.; Porter, Helen G.; Cox, Nancy A.

doi:10.4049/jimmunol.111.5.1407

Cited by 94 publications

(4 citation statements)

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“…However, it inflammation plays an important role in the pathogenesis of CJD [4,[35][36][37]. Typically, prion diseases do not elicit a prominent inflammatory response in the periphery, which can be attributed to the immune tolerance on account of the similar immunogenicity of PrP Sc and PrP C [38]. Nonetheless, several inflammatory markers, such as CRP, IL-6, AAT, α1-acid glycoprotein and fibrinogen, are elevated in the plasma of CJD patients, suggesting that a systematic inflammatory reaction might also associated with pathogenesis of CJD [5,6].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil to High-density Lipoprotein ratio (NHR) as a potential predictor of disease severity and survival time in Creutzfeldt-Jakob disease

et al. 2023

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Introduction Creutzfeldt-Jakob disease (CJD) is a fatal and irreversible neurodegenerative disease. Identification of inexpensive and easy-to-implement biomarkers of CJD which could predict disease severity and patient survival is important for improving disease management. The aim of this study was to assess the predictive value of peripheral neutrophil to lymphocyte ratio (NLR), high-density lipoprotein (HDL), monocyte to HDL ratio (MHR) and neutrophil to HDL ratio (NHR) for CJD. Methods Patients with definite or probable CJD admitted to the Neurology Department of Xuanwu Hospital from 2014 to 2021 were enrolled and followed up until April 2022. Clinical information including sex, age, Barth Index, survival time and results of auxiliary examination were collected, and NLR, HDL, NHR and MHR were measured for all enrolled patients. The associations between NLR, HDL, NHR and MHR, and disease severity (evaluated by Barth Index), survival time and auxiliary examinations were evaluated. Results A total of 88 CJD patients were enrolled and all were deceased. NLR (r = -0.341, p = 0.001), NHR (r = -0.346, p = 0.001) and MHR (r = -0.327, p = 0.002) were significantly associated with disease severity. Higher NHR (HR = 2.344, 95% CI = 1.277–4.303 p = 0.006) and lower HDL (HR = 0.567, 95% CI = 0.346–0.930, p = 0.025) were associated with shorter survival time in the CJD patients. Conclusions Peripheral inflammatory biomarkers, especially NHR, were associated with disease severity and survival duration. These findings provide new insights into the mechanisms and treatment strategies of CJD.

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Section: Discussionmentioning

confidence: 99%

Neutrophil to High-density Lipoprotein ratio (NHR) as a potential predictor of disease severity and survival time in Creutzfeldt-Jakob disease

et al. 2023

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“…PrP C falls within the realm of immune tolerance, and, as the transition to PrP Sc does not involve changes to the polypeptide sequence, this immune privilege also extends to the pathological isoform. With that, most prion infections proceed to their fatal outcomes in the absence of an immune response (Porter et al 1973;Kasper et al 1982). While anti-PrP antibodies have been detected in the end stages of disease (Sassa et al 2010), more typically, the immune system does not perceive, nor respond to, PrP Sc as an infectious threat.…”

Section: Challenges To Developing a Prion Vaccine (Self-tolerance)mentioning

confidence: 99%

Vaccines for prion diseases: a realistic goal?

Napper

Schätzl

2023

Cell Tissue Res

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Prion diseases are fatal infectious neurodegenerative disorders and prototypic conformational diseases, caused by the conformational conversion of the normal cellular prion protein (PrPC) into the pathological PrPSc isoform. Examples are scrapie in sheep and goat, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt–Jacob disease (CJD) in humans. There are no therapies available, and animal prion diseases like BSE and CWD can negatively affect the economy, ecology, animal health, and possibly human health. BSE is a confirmed threat to human health, and mounting evidence supports the zoonotic potential of CWD. CWD is continuously expanding in North America in numbers and distribution and was recently identified in Scandinavian countries. CWD is the only prion disease occurring both in wild and farmed animals, which, together with extensive shedding of infectivity into the environment, impedes containment strategies. There is currently a strong push to develop vaccines against CWD, including ones that can be used in wildlife. The immune system does not develop a bona fide immune response against prion infection, as PrPC and PrPSc share an identical protein primary structure, and prions seem not to represent a trigger for immune responses. This asks for alternative vaccine strategies, which focus on PrPC-directed self-antibodies or exposure of disease-specific structures and epitopes. Several groups have established a proof-of-concept that such vaccine candidates can induce some levels of protective immunity in cervid and rodent models without inducing unwanted side effects. This review will highlight the most recent developments and discuss progress and challenges remaining.

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“…Microglial and astrocyte cell activation is a key feature in many neurodegenerative diseases. Prion diseases are disorders that do not present a typical immune or inflammatory response [101], and it has not been elucidated whether the activation of these mechanisms contributes to the neurodegeneration process or appears as a consequence of the pathogenesis of these diseases [102]. However, neuroinflammation phenomena have been widely reported in these disorders [103], and, therefore, the potential of glial activation and neuroinflammation biomarkers in prion diseases has also been assessed.…”

Section: Ylk-40mentioning

confidence: 99%

Diagnosis in Scrapie: Conventional Methods and New Biomarkers

Sola,

Betancor,

Marco Lorente

et al. 2023

Pathogens

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Scrapie, a naturally occurring prion disease affecting goats and sheep, comprises classical and atypical forms, with classical scrapie being the archetype of transmissible spongiform encephalopathies. This review explores the challenges of scrapie diagnosis and the utility of various biomarkers and their potential implications for human prion diseases. Understanding these biomarkers in the context of scrapie may enable earlier prion disease diagnosis in humans, which is crucial for effective intervention. Research on scrapie biomarkers bridges the gap between veterinary and human medicine, offering hope for the early detection and improved management of prion diseases.

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Failure to Demonstrate a Humoral Immune Response to Scrapie Infection in Mice

Cited by 94 publications

References 0 publications

Neutrophil to High-density Lipoprotein ratio (NHR) as a potential predictor of disease severity and survival time in Creutzfeldt-Jakob disease

Neutrophil to High-density Lipoprotein ratio (NHR) as a potential predictor of disease severity and survival time in Creutzfeldt-Jakob disease

Vaccines for prion diseases: a realistic goal?

Diagnosis in Scrapie: Conventional Methods and New Biomarkers

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