1887

Abstract

Sensitive and specific detection of abnormal prion protein in blood could provide a diagnostic test or screening assay for animal and human prion diseases. Here, the application of an immunocapillary electrophoresis (ICE) method developed for sheep scrapie to brain, spleen and blood from patients with Creutzfeldt–Jakob disease (CJD) is described. The assay involves organic-solvent extraction, a competitive immunoassay using fluorescently labelled synthetic prion protein peptides and polyclonal antibodies specific for those sequences, and analysis by capillary electrophoresis using laser-induced fluorescence detection. The test was evaluated by using clinical blood specimens from patients with variant (=5) or sporadic (=4) CJD and patients initially suspected of having CJD who were given an alternative diagnosis (=6). In this context, the ICE assay was specific, but incompletely sensitive (55 %). The method was unable to detect abnormal prion protein in variant CJD brain or spleen reference materials due to its loss during the extraction process.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81935-0
2006-10-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/10/3119.html?itemId=/content/journal/jgv/10.1099/vir.0.81935-0&mimeType=html&fmt=ahah

References

  1. Barletta J. M., Edelman D. C., Highsmith W. E., Constantine N. T. 2005; Detection of ultra-low levels of pathologic prion protein in scrapie infected hamster brain homogenates using real-time immuno-PCR. J Virol Methods 127:154–164 [CrossRef]
    [Google Scholar]
  2. Bellon A., Seyfert-Brandt W., Lang W., Baron H., Gröner A., Vey M. 2003; Improved conformation-dependent immunoassay: suitability for human prion detection with enhanced sensitivity. J Gen Virol 84:1921–1925 [CrossRef]
    [Google Scholar]
  3. Blajchman M. A., Goldman M., Webert K. E., Vamvakas E. C., Hannon J., Delage G. 2004; Proceedings of a consensus conference: the screening of blood donors for variant CJD. Transfus Med Rev 18:73–92 [CrossRef]
    [Google Scholar]
  4. Brown P., Cervenakova L. 2004; The modern landscape of transfusion-related iatrogenic Creutzfeldt-Jakob disease and blood screening tests. Curr Opin Hematol 11:351–356 [CrossRef]
    [Google Scholar]
  5. Bruce M. E., McConnell I., Will R. G., Ironside J. W. 2001; Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues. Lancet 358:208–209 [CrossRef]
    [Google Scholar]
  6. Cervenakova L., Brown P., Soukharev S., Yakovleva O., Diringer H., Saenko E. L., Drohan W. N. 2003; Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt-Jakob disease. Electrophoresis 24:853–859 [CrossRef]
    [Google Scholar]
  7. Grosset A., Moskowitz K., Nelsen C., Pan T., Davidson E., Orser C. S. 2005; Rapid presymptomatic detection of PrPSc via conformationally responsive palindromic PrP peptides. Peptides 26:2193–2200 [CrossRef]
    [Google Scholar]
  8. Haïk S., Faucheux B. A., Sazdovitch V., Privat N., Kemeny J.-L., Perret-Liaudet A., Hauw J.-J. 2003; The sympathetic nervous system is involved in variant Creutzfeldt-Jakob disease. Nat Med 9:1121–1123 [CrossRef]
    [Google Scholar]
  9. Head M. W., Bunn T. J. R., Bishop M. T. & 9 other authors (2004a). Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: U.K. cases 1991-2002. Ann Neurol 55:851–859 [CrossRef]
    [Google Scholar]
  10. Head M. W., Ritchie D., Smith N. & 7 other authors 2004b; Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease. Am J Pathol 164:143–153 [CrossRef]
    [Google Scholar]
  11. Hilton D. A., Fathers E., Edwards P., Ironside J. W., Zajicek J. 1998; Prion immunoreactivity in appendix before clinical onset of variant Creutzfeldt-Jakob disease. Lancet 352:703–704 [CrossRef]
    [Google Scholar]
  12. Hilton D. A., Ghani A. C., Conyers L., Edwards P., McCardle L., Penney M., Ritchie D., Ironside J. W. 2002; Accumulation of prion protein in tonsil and appendix: review of tissue samples. BMJ 325:633–634 [CrossRef]
    [Google Scholar]
  13. Hilton D. A., Ghani A. C., Conyers L., Edwards P., McCardle L., Ritchie D., Penney M., Hegazy D., Ironside J. W. 2004; Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 203:733–739 [CrossRef]
    [Google Scholar]
  14. HPA 2006; New case of transfusion-associated variant-CJD. In CDR Weekly vol. 16, no. 6: http://www.hpa.org.uk/cdr/archives/archive06/News/news0606.htm
    [Google Scholar]
  15. Hunter N., Foster J., Chong A., McCutcheon S., Parnham D., Eaton S., MacKenzie C., Houston F. 2002; Transmission of prion diseases by blood transfusion. J Gen Virol 83:2897–2905
    [Google Scholar]
  16. Jackman R., Schmerr M. J. 2003; Analysis of the performance of antibody capture methods using fluorescent peptides with capillary zone electrophoresis with laser-induced fluorescence. Electrophoresis 24:892–896 [CrossRef]
    [Google Scholar]
  17. Jackman R., Everest D. J., Schmerr M. J., Khawaja R., Keep P., Docherty J. 2006; Evaluation of a preclinical blood test for scrapie in sheep using immunocapillary electrophoresis. J Assoc Off Anal Chem 89:720–727
    [Google Scholar]
  18. Johnson T. R., Alter H. J., Cliver D. O. & 12 other authors 2001; Testing blood for evidence of the agents of transmissible spongiform encephalopathies. In Advancing Prion Science: Guidance for the National Prion Research Program pp  108–124 Edited by Erdtmann L. R., Sivitz L. B. Washington, DC: National Academies Press;
    [Google Scholar]
  19. Lane A., Oliver J., Quarterman E., Stanley C., Dealler S., Wilson S. 2004; Detection of transmissible spongiform encephalopathies in blood. In Proceedings of the First International Conference of the Network of Excellence NeuroPrion p– 51 Edited by Deslys J. P., Lasmezas C. I., Schell J., Simoneau S.
    [Google Scholar]
  20. Llewelyn C. A., Hewitt P. E., Knight R. S. G., Amar K., Cousens S., Mackenzie J., Will R. G. 2004; Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363:417–421 [CrossRef]
    [Google Scholar]
  21. Minor P. D. 2004; Technical aspects of the development and validation of tests for variant Creutzfeldt-Jakob disease in blood transfusion. Vox Sang 86:164–170 [CrossRef]
    [Google Scholar]
  22. Minor P., Newham J., Jones N. & 9 other authors 2004; Standards for the assay of Creutzfeldt–Jakob disease specimens. J Gen Virol 85:1777–1784 [CrossRef]
    [Google Scholar]
  23. Peden A. H., Head M. W., Ritchie D. L., Bell J. E., Ironside J. W. 2004; Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364:527–529 [CrossRef]
    [Google Scholar]
  24. Safar J. G., Scott M., Monaghan J. & 12 other authors 2002; Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice. Nat Biotechnol 20:1147–1150 [CrossRef]
    [Google Scholar]
  25. Schmerr M. J., Jenny A. 1998; A diagnostic test for scrapie-infected sheep using a capillary electrophoresis immunoassay with fluorescent-labeled peptides. Electrophoresis 19:409–414 [CrossRef]
    [Google Scholar]
  26. Schmerr M. J., Alpert A. J. 2000; Method and kit for extracting prion protein . US patent 6,150,172
  27. Schmerr M. J., Jenny A. L., Bulgin M. S., Miller J. M., Hamir A. N., Cutlip R. C., Goodwin K. R. 1999; Use of capillary electrophoresis and fluorescent labeled peptides to detect the abnormal prion protein in the blood of animals that are infected with a transmissible spongiform encephalopathy. J Chromatogr A 853:207–214 [CrossRef]
    [Google Scholar]
  28. Soto C. 2004; Diagnosing prion diseases: needs, challenges and hopes. Nat Rev Microbiol 2:809–819 [CrossRef]
    [Google Scholar]
  29. Wadsworth J. D. F., Joiner S., Hill A. F., Campbell T. A., Desbruslais M., Luthert P. J., Collinge J. 2001; Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358:171–180 [CrossRef]
    [Google Scholar]
  30. Will R. G., Ironside J. W., Zeidler M. & 7 other authors 1996; A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925 [CrossRef]
    [Google Scholar]
  31. Yakovleva O., Janiak A., McKenzie C., McShane L., Brown P., Cervenakova L. 2004; Effect of protease treatment on plasma infectivity in variant Creutzfeldt-Jakob disease mice. Transfusion 44:1700–1705 [CrossRef]
    [Google Scholar]
  32. Yang W.-C., Yeung E. S., Schmerr M. J. 2005a; Detection of prion protein using a capillary electrophoresis-based competitive immunoassay with laser-induced fluorescence detection and cyclodextrin-aided separation. Electrophoresis 26:1751–1759 [CrossRef]
    [Google Scholar]
  33. Yang W.-C., Schmerr M. J., Jackman R., Bodemer W., Yeung E. S. 2005b; Capillary electrophoresis-based noncompetitive immunoassay for the prion protein using fluorescein-labeled protein A as a fluorescent probe. Anal Chem 77:4489–4494 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81935-0
Loading
/content/journal/jgv/10.1099/vir.0.81935-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error