Title | Plasma protein biosignatures for detection of cardiac allograft vasculopathy. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Lin, D, Freue, GCohen, Hollander, Z, Mancini, GBJohn, Sasaki, M, Mui, A, Wilson-McManus, J, Ignaszewski, A, Imai, C, Meredith, A, Balshaw, R, Ng, RT, Keown, PA, W McMaster, R, Carere, R, Webb, JG, McManus, BM |
Corporate Authors | Biomarkers in Transplantation Team, Networks of Centres of Excellence, Centres of Excellence for Commercialization and Research-Prevention of Organ Failure Centre of Excellence |
Journal | J Heart Lung Transplant |
Volume | 32 |
Issue | 7 |
Pagination | 723-33 |
Date Published | 2013 Jul |
ISSN | 1557-3117 |
Keywords | Blood Proteins, Female, Heart Transplantation, Humans, Male, Middle Aged, Proteomics, Transplantation, Homologous, Vascular Diseases |
Abstract | 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. |
DOI | 10.1016/j.healun.2013.04.011 |
Alternate Journal | J. Heart Lung Transplant. |
PubMed ID | 23796154 |
Grant List | / / Canadian Institutes of Health Research / Canada |