Journal
JOURNAL OF HEART AND LUNG TRANSPLANTATION
Volume 32, Issue 7, Pages 723-733Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2013.04.011
Keywords
proteomic biomarker panels; coronary angiography; cardiac allograft vasculopathy
Funding
- Networks of Centres of Excellence
- Centres of Excellence for Commercialization and Research
- Prevention of Organ Failure Centre of Excellence
- Genome Canada
- Novartis Pharma
- IBM
- Genome British Columbia
- Astellas
- Eksigent
- Vancouver Hospital Foundation
- St. Paul's Hospital Foundation
- University of British Columbia VP Research
- University of British Columbia James Hogg Research Centre
- British Columbia Transplant
- Canadian Institutes of Health Research
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BACKGROUND: Coronary angiography remains the most widely used tool for routine screening and diagnosis of cardiac allograft vasculopathy (CAV), a major pathologic process that develops in 50% of cardiac transplant recipients beyond the first year after transplant. Given the invasiveness, expense, discomfort, and risk of complications associated with angiography, a minimally invasive alternative that is sensitive and specific would be highly desirable for monitoring CAV in patients. METHODS: Plasma proteomic analysis using isobaric tags for relative and absolute quantitation matrix-assisted laser desorption ionization double time-of-flight mass spectrometry was carried out on samples from 40 cardiac transplant patients (10 CAV, 9 non-significant CAV, 21 possible CAV). Presence of CAV was defined as left anterior descending artery diameter stenosis >= 40% by digital angiography and quantitatively measured by blinded expert appraisal. Moderated t-test robust-linear models for microarray data were used to identify biomarkers that are significantly differentially expressed between patient samples with CAV and with non-significant CAV. A proteomic panel for diagnosis of CAV was generated using the Elastic Net classification method. RESULTS: We identified an 18-plasma protein biomarker classifier panel that was able to classify and differentiate patients with angiographically significant CAV from those without significant CAV, with an 80% sensitivity and 89% specificity, while providing insight into the possible underlying immune and non-alloimmune contributory mechanisms of CAV. CONCLUSION: Our results support of the potential utility of proteomic biomarker panels as a minimally invasive means to identify patients with significant, angiographically detectable coronary artery stenosis in the cardiac allograft, in the context of post-cardiac transplantation monitoring and screening for CAV. The potential biologic significance of the biomarkers identified may also help improve our understanding of CAV pathophysiology. J Heart Lung Transplant 2013;32:723-733 (C) 2013 International Society for Heart and Lung Transplantation. An rights reserved.
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