Single Cell Transcriptomics Reveal Allograft Immune Cell Patterns Associated with Histological Features of Acute Cellular Rejection in Liver Transplantation
1Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, 2University of Pittsburgh Medical Center, Pittsburgh, PA, 3University of Pittsburgh Medical Center - Thomas E. Starzl Transplantation Institute, Pittsburgh, PA
Meeting: 2022 American Transplant Congress
Abstract number: 1567
Keywords: Liver transplantation, Outcome, Rejection
Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes
Session Information
Session Name: Biomarkers: Clinical Outcomes
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Development of successful tolerance induction strategies using immune cell-based therapies in transplantation depends on improved understanding of the local intra-graft cellular milieu that underlies graft injury and survival. In an ongoing phase I/II clinical study assessing regulatory dendritic cell (DCreg) therapy in living donor liver transplantation, we aim to detect unique intra-graft immune cell patterns that may correlate with risk of acute cellular rejection (ACR).
*Methods: Allograft tissue biopsies were obtained from enrolled liver transplant recipients on day of transplant (Day 0; post-reperfusion) (n =4 patients) and 1-year post-transplant (n=8). Patient samples were divided based on presence or absence of histological features meeting criteria for ACR on 1-year protocol biopsy. Single-cell RNA sequencing was performed using the 10X Genomics platform. Unsupervised clustering, differential gene expression testing, and enriched pathway analysis was performed.
*Results: A significantly higher proportion of infiltrating neutrophils was detected in allograft tissue taken on Day 0 from patients subsequently exhibiting ACR at 1 year compared to non-ACR patients (33.5% vs. 5.6%, P <0.01), while more intra-graft NK cells and macrophages were detected in non-ACR patients. Myeloid cells in ACR biopsies exhibited an upregulation of genes associated with IL-12 and TNF-alpha signaling. At 1-year post-transplant, higher numbers of B cells and CD8+ T cells were detected in allografts exhibiting features of ACR compared to non-ACR. In addition, upregulation of genes associated with chemokine and IFN-gamma signaling pathways was detected in intra-graft macrophages and NK cells of ACR patients.
*Conclusions: Upregulation of acute-phase cell subsets and signaling pathways are readily identified by single cell transcriptomics in allografts exhibiting ACR which may serve as a predictive biomarker for success of immunosuppressive drug withdrawal/tolerance after liver transplantation.
To cite this abstract in AMA style:
Tran L, Zahorchak A, Macedo C, Tabib T, Lakkis F, Humar A, Metes D, Thomson A. Single Cell Transcriptomics Reveal Allograft Immune Cell Patterns Associated with Histological Features of Acute Cellular Rejection in Liver Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/single-cell-transcriptomics-reveal-allograft-immune-cell-patterns-associated-with-histological-features-of-acute-cellular-rejection-in-liver-transplantation/. Accessed May 6, 2025.« Back to 2022 American Transplant Congress