Journal article
Clinical implications and longitudinal alteration of peripheral blood transcriptional signals indicative of future cardiac allograft rejection
The Journal of heart and lung transplantation, v 27(3)
01 Mar 2008
PMID: 18342752
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: we have previously demonstrated that a peripheral blood transcriptional profile using 11 distinct genes predicts onset of cardiac allograft rejection weeks to months prior to the actual event.
Methods: In this analysis, we ascertained the performance of this transcriptional algorithm in a Bayesian representative population: 28 cardiac transplant recipients who progressed to moderate to severe rejection; 53 who progressed to mild rejection; and 46 who remained rejection-free. Furthermore, we characterized longitudinal alterations in the transcriptional gene expression profile before, during and after recovery from rejection.
Results: In this patient cohort, we found that a gene expression score (range 0 to 40) of <= 20 represents very low risk of rejection in the subsequent 12 weeks: 0 progressed to treatable (ISHLT Grade >= 3A) rejection; 16 of 53 (30%) from the intermediate group (those who progressed to ISHLT Grade 1B or 2) and 13 of 46 (28%) controls (who remained Grade 0 or 1A) had scores <= 20. A gene score of >= 30 was associated with progression to moderate to severe rejection in 58% of cases. These two extreme scores (<= 20 or >= 30) represented 44% of the cardiac transplant population within 6 months post-transplant. In addition, longitudinal gene expression analysis demonstrated that baseline scores were significantly higher for those who went on to reject, remained high during an episode of rejection, and dropped post-treatment for rejection (p < 0.01).
Conclusions: The use of gene expression profiling early after transplantation allows for separation into low-, intermediate- or high-risk categories for future rejection, permitting development of discrete surveillance strategies.
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Details
- Title
- Clinical implications and longitudinal alteration of peripheral blood transcriptional signals indicative of future cardiac allograft rejection
- Creators
- Mandeep R. Mehra - University of Maryland, BaltimoreJon A. Kobashigawa - Center of Mathematical Sciences, Zhejiang UniversityMario C. Deng - Columbia UniversityKenneth C. Fang - XDx, Inc., Brisbane, CaliforniaTod M. Klingler - XDx, Inc., Brisbane, CaliforniaPreeti G. Lal - XDx, Inc., Brisbane, CaliforniaSteven Rosenberg - XDx, Inc., Brisbane, CaliforniaPatricia A. Uber - University of Maryland, BaltimoreRandall C. Starling - Cleveland ClinicSrinivas Murali - Allegheny General HospitalDaniel F. Pauly - University of FloridaRussell Dedrick - XDx, Inc., Brisbane, CaliforniaMichael G. Walker - XDx, Inc., Brisbane, CaliforniaAdriana Zeevi - University of PittsburghHoward J. Eisen - Drexel UniversityCARGO Investigators
- Publication Details
- The Journal of heart and lung transplantation, v 27(3)
- Publisher
- Elsevier
- Number of pages
- 5
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Medicine (Graduate)
- Web of Science ID
- WOS:000254325100009
- Scopus ID
- 2-s2.0-40649093305
- Other Identifier
- 991019167691204721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Respiratory System
- Surgery
- Transplantation