Document Detail


Whole blood biomarkers of acute cardiac allograft rejection: double-crossing the biopsy.
MedLine Citation:
PMID:  21076371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Acute rejection is still a significant barrier to long-term survival of the allograft. Current acute rejection diagnostic methods are not specific enough or are invasive. There have been a number of studies that have explored the blood or the biopsy to discover genomic biomarkers of acute rejection; however, none of the studies to date have used both.
METHODS: We analyzed endomyocardial biopsy tissue and whole blood-derived messenger RNA from 11 acute rejection and 20 nonrejection patients using Affymetrix Human Genome U133 Plus 2.0 chips. We used a novel approach and gained insight into the biology of rejection based on gene expression in the biopsy, and applied this knowledge to the blood analysis to identify novel blood biomarkers.
RESULTS: We identified probesets that are differentially expressed between acute rejection and nonrejection patients in the biopsy and blood, and developed three biomarker panels: (1) based on biopsy-only (area under the curve=0.85), (2) based on biopsy-targeted whole blood (area under the curve=0.83), and (3) based on whole blood-only (area under the curve=0.60) analyses.
CONCLUSIONS: Most of the probesets replicated between biopsy and blood are regulated in opposite direction between the two sources of information. We also observed that the biopsy-targeted blood biomarker discovery approach can improve performance of the biomarker panel. The biomarker panel developed using this targeted approach is able to diagnose acute cardiac allograft rejection almost as well as the biopsy-only based biomarker panel.
Authors:
Zsuzsanna Hollander; David Lin; Virginia Chen; Raymond Ng; Janet Wilson-McManus; Andrew Ignaszewski; Gabriela Cohen Freue; Rob Balshaw; Alice Mui; Robert McMaster; Paul A Keown; Bruce M McManus;
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  90     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1388-93     Citation Subset:  IM    
Affiliation:
NCE CECR PROOF Centre of Excellence, Vancouver, BC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adult
Aged
Area Under Curve
Biological Markers / blood*
Biopsy
Cardiomyopathies / surgery
Female
Heart Transplantation / pathology*
Humans
Male
Middle Aged
Myocardial Ischemia / surgery
Oligonucleotide Array Sequence Analysis
RNA, Messenger / blood,  genetics
Transplantation, Homologous / pathology
Chemical
Reg. No./Substance:
0/Biological Markers; 0/RNA, Messenger

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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