Pre-Transplant Multidimensional Flow Cytometric Analysis of Kidney Transplant Recipients Reveals Novel Immune Signature of Allograft Rejection
1Department of Surgery, Duke University Medical Center, Durham, NC, 2Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 3Substrate Services Core and Research Support, Duke University Medical Center, Durham, NC
Meeting: 2019 American Transplant Congress
Abstract number: B75
Keywords: Kidney transplantation, Rejection
Session Information
Session Name: Poster Session B: Biomarkers, Immune Monitoring and Outcomes
Session Type: Poster Session
Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Multicolor flow cytometry and multiplex assay platforms have revolutionized immune cell phenotyping and functional analyses, but these powerful tools have not demonstrated clinically meaningful biomarkers of allograft rejection in transplant recipients. The purpose of this immune profiling effort was to identify predictive blood-based biomarkers that identify kidney transplant recipients who are at risk for rejection.
*Methods: We retrospectively analyzed serum and peripheral blood mononuclear cells (PBMCs) from 52 kidney transplant recipients and divided them into two groups: those with biopsy proven rejection episodes (Rejection; n=22) and those with no evidence of rejection >1 year post-transplant (No Rejection; n=30). Pre-transplant blood samples were then compared between the Rejection and No Rejection groups.
*Results: A Luminex-based multiplex analysis of 34 cytokines in serum samples revealed 12 cytokines with measureable quantities but no statistically significant differences between the Rejection and No Rejection groups. Multicolor flow cytometric analysis of PBMCs revealed significantly increased ratio of CD8+ to CD4+ T cells in the Rejection group (Figure A, p<0.05). The CD4+ T cells also included a higher proportion of IL21-producing T cells in the Rejection group (Figure B, p<0.05). The CD8+ T cells consisted of an increased proportion of CD38+ T cells in the Rejection group (Figure C, p<0.05). Multidimensional analysis of these CD8+CD38+ T cells revealed them to be terminal effector cells, but not exhausted based on the lack of CD39 and TIM-3 expression.
*Conclusions: This retrospective multidimensional analysis of pre-transplant blood samples revealed a novel immune signature of rejection in a cohort of kidney transplant recipients that consisted of a reversal of the CD4/CD8 cell ratio, increased IL21-producing CD4 cells, and an increase in a specific population of CD8+CD38+ terminal effector cells. These results may direct us toward a novel immune phenotype of patients at risk for rejection that could lead to more personalized care for kidney transplant recipients.
To cite this abstract in AMA style:
Schroder P, Yi JS, Weinhold KJ, Chan C, Joshi M, Walters C, Kwun J, Knechtle SJ. Pre-Transplant Multidimensional Flow Cytometric Analysis of Kidney Transplant Recipients Reveals Novel Immune Signature of Allograft Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/pre-transplant-multidimensional-flow-cytometric-analysis-of-kidney-transplant-recipients-reveals-novel-immune-signature-of-allograft-rejection/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress