Tonsillar biopsy and PrP<sup>Sc</sup> detection in the preclinical diagnosis of scrapie

Schreuder, B. E. C.; Keulen, L.J.M. van; Vromans, M. E. W.; Langeveld, J.P.M.; Smits, M.A.

doi:10.1136/vr.142.21.564

Cited by 170 publications

(103 citation statements)

References 24 publications

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“…After the lag phase, PrP sc accumulates rapidly in lymphoid tissues throughout the body as well as the intestinal nervous supply, which offers the possibility of biopsy-based preclinical diagnosis. 24,25,34,35 On the other hand, preclinical dissemination of PrP sc deposits into the placenta indicates a risk of horizontal and vertical transmission by clinically healthy ewes. The finding that most cases within scrapie-affected flocks are preclinical underscores the significance of observing PrP sc accumulation in the placentas of a high percentage of infected sheep.…”

Section: Discussionmentioning

confidence: 99%

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Caplazi

O’Rourke²,

Wolf

et al. 2004

J VET Diagn Invest

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Abstract. Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrP sc , in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrP sc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrP sc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrP sc deposition in various tissues using single-and dual-label immunohistochemistry. Scrapie, as defined by PrP sc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrP sc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrP sc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrP sc deposition in the brain but widespread PrP sc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrP sc accumulation preceding deposition in the brain. PrP sc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrP sc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrP sc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrP sc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171: PrP sc deposition was restricted to PrP genotype AA 136 RR 154 QQ 171 in 12/13 cases or AV 136 RR 154 QQ 171 in 1/13 cases. The earliest accumulation was observed in the single VRQ/ARQ heterozygous animal, consistent with the reported high scrapie susceptibility and brief incubation period observed in breeds with predominance of the V 136 R 154 Q 171 allele. Disease occurred within, as well as independent of, motherdaughter lines, suggesting both maternal and nonmaternal transmission in the flocks.

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Section: Discussionmentioning

confidence: 99%

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Caplazi

O’Rourke²,

Wolf

et al. 2004

J VET Diagn Invest

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“…Presymptomatic and minimally invasive diagnostic approaches are therefore crucial to enhance the chance of success of any possible interventional approach. It has been shown that PrP Sc could be detected in the tongue of a vCJD patient [82], at preclinical stages in tonsils of sheep infected with scrapie [83] and in human appendices [84], indicating that lymphoid tissue biopsies could in principle be used for early diagnosis of vCJD. In addition, efforts are currently made to develop tests that can detect PrP Sc in blood where its concentration is 100-1000 times lower than in the brain.…”

Section: Diagnostic Reagentsmentioning

confidence: 99%

Probing the origins, diagnosis and treatment of amyloid diseases using antibodies

Dumoulin

Dobson

2004

Biochimie

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The deposition of proteins in the form of amyloid fibrils is the characteristic feature of more than 20 medical conditions affecting the central nervous system or a variety of peripheral tissues. These disorders, which include Alzheimer's disease, the prion diseases and type II diabetes, are of enormous importance in the context of present-day human health and welfare. Extensive research is therefore being carried out to define the molecular details of the mechanism of the pathological conversion of amyloidogenic proteins from their soluble forms into fibrillar structures. This review focuses on recent studies that demonstrate the power of using antibodies or antibody fragments to probe the process of fibril formation, and discusses the emerging potential of these species as diagnostic and therapeutic agents.

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“…Preclinical tests for scrapie in domestic sheep, using biopsy samples of lymphoid tissues from the palatine tonsil, 5 third eyelid, 4 and rectal mucosa, 2,3 have been described. Preclinical diagnostic tests for CWD have been described for mule deer using biopsy tissues of palatine tonsil 10 and rectal mucosa.…”

mentioning

confidence: 99%

Impact of Age and Sex of Rocky Mountain Elk (Cervus Elaphus Nelsoni) on Follicle Counts from Rectal Mucosal Biopsies for Preclinical Detection of Chronic Wasting Disease

Spraker

VerCauteren

Gidlewski³

et al. 2009

J VET Diagn Invest

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Abstract. To determine if the number of rectal lymphoid follicles decreases with respect to age and sex relative to diagnosis of chronic wasting disease (CWD), rectal biopsies (n 5 1,361) were taken from captive Rocky Mountain elk (Cervus elaphus nelsoni) at 4 ranches in the western United States between 2005 and 2008. Rectal tissues were stained with a monoclonal antibody (F99/97.6.1), which selectively stains the abnormal isoform of the prion protein associated with CWD of elk. The number of lymphoid follicles obtained from typical biopsy tissues decreased with the age of the animal. The acceptable number of lymphoid follicles for detection of CWD was not considered to be a problem in elk up to 8.5 years of age, but in elk over 8.5 years of age, the follicle count was considered to be low. Sex of the animal had no effect on the number of lymphoid follicles observed in each age group. Rectal biopsies were an accurate test to diagnose preclinical stages of CWD in elk but may be best suited to elk that are less then 8.5 years of age.

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Tonsillar biopsy and PrP^Sc detection in the preclinical diagnosis of scrapie

Cited by 170 publications

References 24 publications

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Probing the origins, diagnosis and treatment of amyloid diseases using antibodies

Impact of Age and Sex of Rocky Mountain Elk (Cervus Elaphus Nelsoni) on Follicle Counts from Rectal Mucosal Biopsies for Preclinical Detection of Chronic Wasting Disease

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Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie

Cited by 170 publications

References 24 publications

Biology of PrPsc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrPsc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Probing the origins, diagnosis and treatment of amyloid diseases using antibodies

Impact of Age and Sex of Rocky Mountain Elk (Cervus Elaphus Nelsoni) on Follicle Counts from Rectal Mucosal Biopsies for Preclinical Detection of Chronic Wasting Disease

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Tonsillar biopsy and PrP^Sc detection in the preclinical diagnosis of scrapie

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks