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The identification of disease-induced biomarkers in the urine of BSE infected cattle

Sharon LR Simon1 email, Lise Lamoureux1 email, Margot Plews1 email, Michael Stobart1,2 email, Jillian LeMaistre3 email, Ute Ziegler4 email, Catherine Graham5 email, Stefanie Czub5 email, Martin Groschup4 email and J David Knox1,2 email

Prion Diseases Program, Public Health Agency of Canada, Winnipeg, R3E 3P6, Canada

Department of Medical Microbiology, University of Manitoba, Winnipeg, R3E 0W3, Canada

Department of Pharmacology, University of Manitoba, Winnipeg, R2H 2A6, Canada

Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler Institut, 17493 Greifswald-Insel Riems, Germany

Animal Diseases Research Institute, Canadian Food Inspection Agency, Lethbridge, T1J 3Z4, Canada

author email corresponding author email

Proteome Science 2008, 6:23doi:10.1186/1477-5956-6-23

Published: 5 September 2008

Abstract

Background

The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob Disease (vCJD) have led to profound changes in the production and trade of agricultural goods. The rapid tests currently approved for BSE monitoring in slaughtered cattle are all based on the detection of the disease related isoform of the prion protein, PrPd, in brain tissue and consequently are only suitable for post-mortem diagnosis. Objectives: In instances such as assessing the health of breeding stock for export purposes where post-mortem testing is not an option, there is a demand for an ante-mortem test based on a matrix or body fluid that would permit easy access and repeated sampling. Urine and urine based analyses would meet these requirements.

Results

Two dimensional differential gel eletrophoresis (2D-DIGE) and mass spectrometry analyses were used to identify proteins exhibiting differential abundance in the urine of BSE infected cattle and age matched controls over the course of the disease. Multivariate analyses of protein expression data identified a single protein able to discriminate, with 100% accuracy, control from infected samples. In addition, a subset of proteins were able to predict with 85% ± 13.2 accuracy the time post infection that the samples were collected.

Conclusion

These results suggest that in principle it is possible to identify biomarkers in urine useful in the diagnosis, prognosis and monitoring of disease progression of transmissible spongiform encephalopathy diseases (TSEs).


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