Preclinical Diagnosis of Scrapie by Immunohistochemistry of Third Eyelid Lymphoid Tissue

Overview

Journal J Clin Microbiol

Specialty Microbiology

Date 2000 Sep 2

PMID 10970367

Citations 82

Authors

K I ORourke

T V Baszler

T E Besser

J M Miller

R C Cutlip

G A Wells

S J Ryder

S M Parish

A N Hamir

N E Cockett

A Jenny

D P Knowles

Affiliations

Soon will be listed here.

Abstract

Ovine scrapie is a member of the transmissible spongiform encephalopathies (TSEs), a heterogeneous family of fatal neurologic disorders characterized by deposition of an abnormal isoform (prion protein [PrP] PrP-Sc) of a cellular sialoglycoprotein in neural tissue. PrP-Sc is detectable in some lymphoid tissues of infected sheep months or years before development of clinical disease. Detection of PrP-Sc in these tissues is the basis for live-animal testing. In this study, we characterize the performance of a preclinical diagnostic test for ovine scrapie based on a monoclonal antibody (MAb)-based immunohistochemistry assay of nictitating membrane ("third eyelid")-associated lymphoid tissue. The results of third eyelid immunohistochemistry assay agreed with the scrapie status of the sheep for 41 of 42 clinical suspects with confirmed scrapie and 174 of 175 sheep without scrapie. Third eyelid sampling agreed with the scrapie status for 36 of 41 clinically normal sheep positive for PrP-Sc immunostaining of brain tissue, including 27 sheep with positive biopsy specimens that progressed to clinical disease with confirmed scrapie 3 to 20 months after biopsy. The assay used MAb F89/160.1.5, which binds to residues 142 to 145 of ovine PrP. This antibody can be used in combination with MAb F99/97. 6.1, which binds to residues 220 to 225. One or both MAbs in this cocktail recognize PrP sequences conserved in most mammalian species in which natural TSEs have been reported. Immunohistochemistry assay of routinely formalin-fixed lymphoid tissues with a cocktail of pan-specific MAbs is a practical, readily standardized live-animal and preclinical test for ovine scrapie.

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References

ORourke K, Holyoak G, Clark W, Mickelson J, Wang S, Melco R . PrP genotypes and experimental scrapie in orally inoculated Suffolk sheep in the United States. J Gen Virol. 1997; 78 ( Pt 4):975-8. DOI: 10.1099/0022-1317-78-4-975. View

Wells G, Hawkins S, Green R, Austin A, Dexter I, Spencer Y . Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet Rec. 1998; 142(5):103-6. DOI: 10.1136/vr.142.5.103. View

ORourke K, Baszler T, Parish S, Knowles D . Preclinical detection of PrPSc in nictitating membrane lymphoid tissue of sheep. Vet Rec. 1998; 142(18):489-91. DOI: 10.1136/vr.142.18.489. View

ORourke K, Baszler T, Miller J, Spraker T, Knowles D . Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. J Clin Microbiol. 1998; 36(6):1750-5. PMC: 104913. DOI: 10.1128/JCM.36.6.1750-1755.1998. View

Schreuder B, van Keulen L, Vromans M, Langeveld J, Smits M . Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie. Vet Rec. 1998; 142(21):564-8. DOI: 10.1136/vr.142.21.564. View

Bons N, Mestre-Frances N, Belli P, Cathala F, Gajdusek D, Brown P . Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents. Proc Natl Acad Sci U S A. 1999; 96(7):4046-51. PMC: 22417. DOI: 10.1073/pnas.96.7.4046. View

Prusiner S . Novel proteinaceous infectious particles cause scrapie. Science. 1982; 216(4542):136-44. DOI: 10.1126/science.6801762. View

Hadlow W, Kennedy R, Race R . Natural infection of Suffolk sheep with scrapie virus. J Infect Dis. 1982; 146(5):657-64. DOI: 10.1093/infdis/146.5.657. View

Kitamoto T, Ogomori K, Tateishi J, Prusiner S . Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest. 1987; 57(2):230-6. View

10.

Wells G, Scott A, Johnson C, Gunning R, Hancock R, Jeffrey M . A novel progressive spongiform encephalopathy in cattle. Vet Rec. 1987; 121(18):419-20. DOI: 10.1136/vr.121.18.419. View

11.

Aldhous P . BSE: spongiform encephalopathy found in cat. Nature. 1990; 345(6272):194. DOI: 10.1038/345194c0. View

12.

Ikegami Y, Ito M, Isomura H, Momotani E, Sasaki K, Muramatsu Y . Pre-clinical and clinical diagnosis of scrapie by detection of PrP protein in tissues of sheep. Vet Rec. 1991; 128(12):271-5. DOI: 10.1136/vr.128.12.271. View

13.

Guiroy D, Williams E, Yanagihara R, Gajdusek D . Immunolocalization of scrapie amyloid (PrP27-30) in chronic wasting disease of Rocky Mountain elk and hybrids of captive mule deer and white-tailed deer. Neurosci Lett. 1991; 126(2):195-8. DOI: 10.1016/0304-3940(91)90552-5. View

14.

Williams E, Young S . Spongiform encephalopathies in Cervidae. Rev Sci Tech. 1992; 11(2):551-67. DOI: 10.20506/rst.11.2.611. View

15.

Race R, Ernst D, Jenny A, Taylor W, Sutton D, Caughey B . Diagnostic implications of detection of proteinase K-resistant protein in spleen, lymph nodes, and brain of sheep. Am J Vet Res. 1992; 53(6):883-9. View

16.

Wells G, Mcgill I . Recently described scrapie-like encephalopathies of animals: case definitions. Res Vet Sci. 1992; 53(1):1-10. DOI: 10.1016/0034-5288(92)90076-e. View

17.

McBride P, Eikelenboom P, Kraal G, Fraser H, Bruce M . PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol. 1992; 168(4):413-8. DOI: 10.1002/path.1711680412. View

18.

Miller J, Jenny A, Taylor W, Marsh R, Rubenstein R, Race R . Immunohistochemical detection of prion protein in sheep with scrapie. J Vet Diagn Invest. 1993; 5(3):309-16. DOI: 10.1177/104063879300500301. View

19.

Haritani M, Spencer Y, Wells G . Hydrated autoclave pretreatment enhancement of prion protein immunoreactivity in formalin-fixed bovine spongiform encephalopathy-affected brain. Acta Neuropathol. 1994; 87(1):86-90. DOI: 10.1007/BF00386258. View

20.

Westaway D, Zuliani V, Cooper C, Da Costa M, Neuman S, Jenny A . Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev. 1994; 8(8):959-69. DOI: 10.1101/gad.8.8.959. View