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 Citations (Scopus)

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 2004
Externally publishedYes

Fingerprint

Biopsy
Proteomics
Allografts
Tropomyosin
Crystallins
Blood
Transplants
Electrophoresis, Gel, Two-Dimensional
Heart Transplantation
Heat-Shock Proteins
Electrophoresis
Serum
Assays
Biomarkers
Gels
Enzyme-Linked Immunosorbent Assay
Molecules
Proteins

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Borozdenkova, S., Westbrook, J. A., Patel, V., Wait, R., Bolad, I., Burke, M. M., ... 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

Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection. / Borozdenkova, Svetlana; Westbrook, Jules A.; Patel, Vaksha; Wait, Robin; Bolad, Islam; Burke, Margaret M.; Bell, Alexander D.; Banner, Nicholas R.; Dunn, Michael J.; Rose, Marlene L.

In: Journal of Proteome Research, Vol. 3, No. 2, 03.2004, p. 282-288.

Research output: Contribution to journalArticle

Borozdenkova, S, Westbrook, JA, Patel, V, Wait, R, Bolad, I, Burke, MM, Bell, AD, Banner, NR, Dunn, MJ & Rose, ML 2004, 'Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection', Journal of Proteome Research, vol. 3, no. 2, pp. 282-288. https://doi.org/10.1021/pr034059r
Borozdenkova, Svetlana ; Westbrook, Jules A. ; Patel, Vaksha ; Wait, Robin ; Bolad, Islam ; Burke, Margaret M. ; Bell, Alexander D. ; Banner, Nicholas R. ; Dunn, Michael J. ; Rose, Marlene L. / Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection. In: Journal of Proteome Research. 2004 ; Vol. 3, No. 2. pp. 282-288.
@article{cfcf23df8519420e9648ad2355a9259b,
title = "Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection",
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.",
keywords = "Allograft, Heart, Markers of rejection, Rejection, Transplant rejection, Transplantation",
author = "Svetlana Borozdenkova and Westbrook, {Jules A.} and Vaksha Patel and Robin Wait and Islam Bolad and Burke, {Margaret M.} and Bell, {Alexander D.} and Banner, {Nicholas R.} and Dunn, {Michael J.} and Rose, {Marlene L.}",
year = "2004",
month = "3",
doi = "10.1021/pr034059r",
language = "English (US)",
volume = "3",
pages = "282--288",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Use of Proteomics to Discover Novel Markers of Cardiac Allograft Rejection

AU - Borozdenkova, Svetlana

AU - Westbrook, Jules A.

AU - Patel, Vaksha

AU - Wait, Robin

AU - Bolad, Islam

AU - Burke, Margaret M.

AU - Bell, Alexander D.

AU - Banner, Nicholas R.

AU - Dunn, Michael J.

AU - Rose, Marlene L.

PY - 2004/3

Y1 - 2004/3

N2 - 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.

AB - 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.

KW - Allograft

KW - Heart

KW - Markers of rejection

KW - Rejection

KW - Transplant rejection

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=16544372141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16544372141&partnerID=8YFLogxK

U2 - 10.1021/pr034059r

DO - 10.1021/pr034059r

M3 - Article

C2 - 15113105

AN - SCOPUS:16544372141

VL - 3

SP - 282

EP - 288

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -