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Updated: Jan 2, 2026
Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation
Published on: September 6, 2017
Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics
Aws Almufleh1,2, Liyong Zhang3, Lisa M Mielniczuk1
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Insights
Researchers identified 14 novel protein biomarkers for cardiac allograft vasculopathy (CAV) using the SOMAscan assay. These biomarkers show promise for diagnosing and predicting CAV after heart transplantation, aiding long-term patient survival.
Area of Science:
- Cardiology
- Immunology
- Biomarker Discovery
Background:
- Cardiac allograft vasculopathy (CAV) significantly impacts long-term survival post-heart transplantation.
- Current non-invasive diagnostic methods and validated biomarkers for CAV are lacking.
Purpose of the Study:
- To identify novel serum protein biomarkers for the diagnosis and prognostication of CAV.
- To leverage the SOMAscan assay for comprehensive proteomic analysis in heart transplant recipients.
Main Methods:
- SOMAscan assay performed on serum from three patient groups: CAV0 (control), CAV1-2 (mild-moderate CAV), and CAV3 (severe CAV).
- Proteomic data analyzed using one-way ANOVA with a false discovery rate q-value < 0.10.
- Preliminary receiver operating characteristics (ROC) curve analysis to assess biomarker discriminative ability.
Main Results:
- Identified 14 novel candidate protein biomarkers for CAV, with 4 specific to mild-moderate CAV.
- These proteins are involved in key pathways such as apoptosis, inflammation, and platelet/coagulation activation.
- Preliminary ROC analysis indicated moderate-to-high discriminative ability (AUC 0.72-0.94) for the identified biomarkers.
Conclusions:
- The study identified promising novel protein biomarkers for CAV.
- These candidate biomarkers demonstrate potential for non-invasive diagnosis and prognostication of CAV.
- Further validation in prospective studies is underway to confirm their clinical utility.
Abstract:
Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV1-2 (mild-moderate CAV), CAV3 (severe CAV), and CAV0 (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies.
