Blood and Biopsy Genomic Signatures of Acute Rejection in Liver Transplant Recipients.
1Northwestern, Chicago
2The Scripps Research Institute, San Diego
3University of Pittsburgh, Pittsburgh
Meeting: 2017 American Transplant Congress
Abstract number: 572
Keywords: Genomics, Liver transplantation, Rejection
Session Information
Session Name: Concurrent Session: Late Breaking
Session Type: Concurrent Session
Date: Tuesday, May 2, 2017
Session Time: 4:30pm-6:00pm
Presentation Time: 5:42pm-5:54pm
Location: E353C
Background: Biomarker profiles diagnostic of acute rejection (AR) could enhance the diagnosis and management of liver transplant (LT) recipients. Our aim was to identify diagnostic genomic (mRNA) signatures of AR that are distinct from other causes of graft dysfunction.
Methods: LT recipients undergoing biopsies for cause had blood collected for mRNA expression using microarrays. Two pathologists and a hepatologist confirmed the following phenotypes: AR, non-AR (mixed causes of dysfunction not due to AR) and TX (no biopsy but non-viral recipient with normal liver tests for six months before/after blood collection). For the blood analysis, the discovery training set generated a locked classification model for AR vs. other phenotypes and was subjected to two types of internal validation: an leave-one out cross-validation (LOOCV) and bootstrap based error estimate. Using the same approach, biopsy tissue samples underwent discovery of the AR vs. non-AR classifier.
Results: 181 LT recipients (45 TX, 45 AR, 91 non-AR), age 54.8±8.1 years, 62% male, mean 2.9±1.1 years from LT, were analyzed. High predictive accuracies were obtained in differentiating AR from TX and AR from non-AR in blood (table 1). Biopsy tissue profiling (96 LT recipients; 32 AR, 64 non-AR)) also differentiated AR from non-AR with high accuracy. Biological function and canonical pathway mapping of the blood/graft profiles suggest immune/inflammatory genes differentially expressed in recipients with AR vs. the other etiologies.
| AR vs. TX | AR vs. Non-AR | AR vs. Non-AR | |
| mRNA source | Blood | Blood | Biopsy |
| # Classifier Probes | 500 | 229 | 200 |
| Bootstrap Accuracy | 83% | 70% | 85% |
| LOOCV Accuracy | 92% | 80% | 90% |
| Sensitivity | 88.6% | 73.2% | 96% |
| Specificity | 87.5% | 82.7% | 88.6% |
| Negative Predictive Value | 89.4% | 88% | 98.4% |
| Positive Predictive Value | 86.7% | 63.8% | 75% |
Conclusion: We have identified blood and graft mRNA signatures that can distinguish AR from other major causes of graft injury in LT recipients and may be useful in the monitoring and management of LT recipients. Samples from a prospective multicenter LT study (NIAID CTOT-14) will be used to externally validate the diagnostic and predictive value of these signatures.
CITATION INFORMATION: Levitsky J, Whisenant T, Kurian S, Rao S, Demetris A, Abecassis M. Blood and Biopsy Genomic Signatures of Acute Rejection in Liver Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Levitsky J, Whisenant T, Kurian S, Rao S, Demetris A, Abecassis M. Blood and Biopsy Genomic Signatures of Acute Rejection in Liver Transplant Recipients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/blood-and-biopsy-genomic-signatures-of-acute-rejection-in-liver-transplant-recipients/. Accessed November 21, 2024.« Back to 2017 American Transplant Congress