Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection

Svetlana Borozdenkova, Jules A. Westbrook, Vaksha Patel, Robin Wait, Islam Bolad, Margaret M. Burke, Alexander D. Bell, Nicholas R. Banner, Michael J. Dunn, Marlene L. Rose

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Endomyocardial biopsy remains the most reliable method of detecting rejection following cardiac transplantation. Despite numerous attempts to detect rejection using a blood assay, none have proved reliable enough to replace the biopsy. Here, we have investigated the hypothesis that proteomics has the potential to reveal many molecules which are upregulated in the heart during rejection, some of which may serve as novel blood markers of rejection. Initially, sequential cardiac biopsies (33 in total) from 4 patients were analysed by two-dimensional gel electrophoresis according to whether they showed rejection (n = 16) or no rejection (n = 17); over 100 proteins were found to be upregulated by between 2- and 50-fold during rejection. Of these, 13 were identified and were found to be cardiac specific or heat shock proteins. Two of these (αβ-crystallin, tropomyosin) were measured by ELISA in the sera of 17 patients followed for 3 months after their transplants. Mean levels of αβ-crystallin and tropomyosin were significantly higher in sera associated with biopsies showing 1A (p = 0.007) or all grades of rejection (p = 0.022) compared to no rejection. These studies demonstrate that proteomics is a powerful method that can be used to identify novel serum markers of human cardiac allograft rejection.

Original languageEnglish (US)
Pages (from-to)282-288
Number of pages7
JournalJournal of Proteome Research
Volume3
Issue number2
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Keywords

  • Allograft
  • Heart
  • Markers of rejection
  • Rejection
  • Transplant rejection
  • Transplantation

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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  • Cite this

    Borozdenkova, S., Westbrook, J. A., Patel, V., Wait, R., Bolad, I., Burke, M. M., Bell, A. D., Banner, N. R., Dunn, M. J., & Rose, M. L. (2004). Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection. Journal of Proteome Research, 3(2), 282-288. https://doi.org/10.1021/pr034059r