Ovine serum biomarkers of early and late phase scrapie.
BACKGROUND
Transmissible spongiform encephalopathies are fatal neurodegenerative disease occurring in animals and humans for which no ante-mortem diagnostic test in biological fluids is available. In such pathologies, detection of the pathological form of the prion protein (i.e., the causative factor) in blood is difficult and therefore identification of new biomarkers implicated in the pathway of prion infection is relevant.


METHODS
In this study we used the SELDI-TOF MS technology to analyze a large number of serum samples from control sheep and animals with early phase or late phase scrapie. A few potential low molecular weight biomarkers were selected by statistical methods and, after a training analysis, a protein signature pattern, which discriminates between early phase scrapie samples and control sera was identified.


RESULTS
The combination of early phase biomarkers showed a sensitivity of 87% and specificity of 90% for all studied sheep in the early stage of the disease. One of these potential biomarkers was identified and validated in a SELDI-TOF MS kinetic study of sera from Syrian hamsters infected by scrapie, by western blot analysis and ELISA quantitation.


CONCLUSIONS
Differential protein expression profiling allows establishing a TSE diagnostic in scrapie sheep, in the early phase of the disease. Some proteic differences observed in scrapie sheep exist in infected hamsters. Further studies are being performed to identify all the discriminant biomarkers of interest and to test our potential markers in a new cohort of animals.
Complex system modeling and engineering for diagnosis, SysDiag - UMR 3145 CNRS/Bio-Rad, 34184 Montpellier Cedex 4, France. isabelle.molina@sysdiag.cnrs.fr
Isabelle
I
Batxelli-Molina
Nicolas
N
Salvetat
Olivier
O
Andréoletti
Luc
L
Guerrier
Guillaume
G
Vicat
Franck
F
Molina
Chantal
C
Mourton-Gilles
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D006224:Cricetinae; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D008647:Mesocricetus; D015203:Reproducibility of Results; D012608:Scrapie / Q000097:blood*; D012680:Sensitivity and Specificity; D012756:Sheep; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000662:veterinary
D015415:Biomarkers