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Published on: October 31, 2012
Plasma protein biosignatures for detection of cardiac allograft vasculopathy
David Lin1, Gabriela Cohen Freue, Zsuzsanna Hollander
1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 2K5, Canada.
Insights
A new 18-plasma protein panel can identify cardiac allograft vasculopathy (CAV) in heart transplant patients. This minimally invasive test shows promise for routine screening, improving early detection of CAV.
Area of Science:
- Cardiology
- Transplant Medicine
- Proteomics
Background:
- Cardiac allograft vasculopathy (CAV) affects 50% of heart transplant recipients, necessitating routine monitoring.
- Coronary angiography is the standard for CAV diagnosis but is invasive and costly.
- A sensitive and specific minimally invasive alternative for CAV monitoring is highly desirable.
Purpose of the Study:
- To develop and validate a minimally invasive proteomic biomarker panel for diagnosing cardiac allograft vasculopathy (CAV).
- To identify plasma protein biomarkers that differentiate significant CAV from non-significant CAV in heart transplant recipients.
Main Methods:
- Plasma proteomic analysis using MALDI-TOF MS on samples from 40 heart transplant patients.
- Digital angiography defined CAV as ≥40% stenosis in the left anterior descending artery.
- An 18-plasma protein classifier panel was generated using Elastic Net classification.
Main Results:
- An 18-plasma protein panel differentiated patients with significant CAV from those without.
- The panel demonstrated 80% sensitivity and 89% specificity for detecting CAV.
- Biomarkers provided insights into immune and non-alloimmune mechanisms contributing to CAV.
Conclusions:
- Proteomic biomarker panels show potential as a minimally invasive tool for screening and monitoring CAV.
- This approach can identify patients with significant coronary artery stenosis in cardiac allografts.
- The identified biomarkers may enhance understanding of CAV pathophysiology.
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.
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