Whole transcriptome profiling of prospective endomyocardial biopsies reveals prognostic and diagnostic signatures of cardiac allograft rejection.
Piening, Brian D and Dowdell, Alexa K and Zhang, Mengqi and Loza, Bao-Li and Walls, David and Gao, Hui and Mohebnasab, Maede and Li, Yun Rose and Elftmann, Eric and Wei, Eric and Gandla, Divya and Lad, Hetal and Chaib, Hassan and Sweitzer, Nancy K and Deng, Mario and Pereira, Alexandre C and Cadeiras, Martin and Shaked, Abraham and Snyder, Michael P and Keating, Brendan J
(2022)
Whole transcriptome profiling of prospective endomyocardial biopsies reveals prognostic and diagnostic signatures of cardiac allograft rejection.
J Heart Lung Transplant, 41 (6).
840 - 848.
Abstract
BACKGROUND: Heart transplantation provides a significant improvement in survival and quality of life for patients with end-stage heart disease, however many recipients experience different levels of graft rejection that can be associated with significant morbidities and mortality. Current clinical standard-of-care for the evaluation of heart transplant acute rejection (AR) consists of routine endomyocardial biopsy (EMB) followed by visual assessment by histopathology for immune infiltration and cardiomyocyte damage. We assessed whether the sensitivity and/or specificity of this process could be improved upon by adding RNA sequencing (RNA-seq) of EMBs coupled with histopathological interpretation. METHODS: Up to 6 standard-of-care, or for-cause EMBs, were collected from 26 heart transplant recipients from the prospective observational Clinical Trials of Transplantation (CTOT)-03 study, during the first 12-months post-transplant and subjected to RNA-seq (n = 125 EMBs total). Differential expression and random-forest-based machine learning were applied to develop signatures for classification and prognostication. RESULTS: Leveraging the unique longitudinal nature of this study, we show that transcriptional hallmarks for significant rejection events occur months before the actual event and are not visible using traditional histopathology. Using this information, we identified a prognostic signature for 0R/1R biopsies that with 90% accuracy can predict whether the next biopsy will be 2R/3R. CONCLUSIONS: RNA-seq-based molecular characterization of EMBs shows significant promise for the early detection of cardiac allograft rejection.
Share
Citation/Export: |
|
Social Networking: |
|
Details
Item Type: |
Article
|
Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
---|
Piening, Brian D | | | | Dowdell, Alexa K | | | | Zhang, Mengqi | | | | Loza, Bao-Li | | | | Walls, David | | | | Gao, Hui | | | | Mohebnasab, Maede | MAM1236@pitt.edu | MAM1236 | 0000-0001-6623-9514 | Li, Yun Rose | | | | Elftmann, Eric | | | | Wei, Eric | | | | Gandla, Divya | | | | Lad, Hetal | | | | Chaib, Hassan | | | | Sweitzer, Nancy K | | | | Deng, Mario | | | | Pereira, Alexandre C | | | | Cadeiras, Martin | | | | Shaked, Abraham | | | | Snyder, Michael P | | | | Keating, Brendan J | | | |
|
Date: |
25 January 2022 |
Date Type: |
Acceptance |
Journal or Publication Title: |
J Heart Lung Transplant |
Volume: |
41 |
Number: |
6 |
Page Range: |
840 - 848 |
DOI or Unique Handle: |
10.1016/j.healun.2022.01.1377 |
Schools and Programs: |
School of Medicine > Pathology |
Refereed: |
Yes |
Uncontrolled Keywords: |
acute rejection, cardiac allograft, transcriptomics, Allografts, Biopsy, Gene Expression Profiling, Graft Rejection, Heart Transplantation, Humans, Myocardium, Postoperative Complications, Prognosis, Prospective Studies, Quality of Life |
Related URLs: |
|
Funders: |
NIAID NIH HHS (U01 AI152960), NIDDK NIH HHS (F32 DK100072), NIAID NIH HHS (U01 AI063589), NIAID NIH HHS (R01 AI144522), NHLBI NIH HHS (T32 HL098049), NIH HHS (S10 OD020141) |
PubMed Central ID: |
PMC9133065 |
PubMed ID: |
35317953 |
Date Deposited: |
25 Oct 2022 17:51 |
Last Modified: |
28 Jun 2023 08:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/43669 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Altmetric.com
Actions (login required)
 |
View Item |
|