USF-LVHN SELECT
Relationship Between Blood and Tissue-Based Rejection-Related Transcripts in Heart Transplantation.
Publication/Presentation Date
9-18-2023
Abstract
PURPOSE: The purpose of the study is to investigate the relationship between blood and tissue-derived rejection-related transcripts from blood gene expression profiling (GEP) and molecular microscope in the setting of allograft rejection in heart transplant.
METHODS: All heart transplant patients from August 2021 to May 2022 with both circulating blood GEP (AlloMap; CareDx) and endomyocardial biopsy with molecular microscope diagnostic system (MMDx, One Lambda) within 4 weeks were included (N=173 samples). We obtained individual blood GEP-based mRNA transcript expression levels of the 11 target genes from CareDx. Student's t-test was performed to compare blood GEP transcript expression levels between no rejection and rejection as assessed by MMDx. A Scatter plot with Spearman correlation analysis was performed to compare the relationship between transcript expression levels from AlloMap and MMDx, with and without allograft rejection.
RESULTS: There were 52 samples (30.1%) with antibody-mediated rejection (ABMR) and 15 samples (8.7%) with T-cell-mediated rejection (TCMR), as assessed by MMDx. Expression of one of the blood ITGA4 (Integrin alpha 4) expression level was elevated in ABMR, compared to no ABMR (4607.5 vs 4217.5; p=0.019). Most tissue RAT expression levels were elevated in ABMR, and tissue ROBO4 expression correlated with the blood ITGA4 expression with moderate or greater effect size in all samples (Spearman's R 0.31; p
DISCUSSION: Circulating blood ITGA4 expression is elevated in AMR and correlate with myocardial expression of ROBO4. The knowledge of individual transcript expression levels in blood and in tissue may provide insights into various disease processes in heart transplant patients. Taken together, the results of our study reveal an overlap between two objective post-heart transplant rejection surveillance methods, identify potential novel markers for ABMR, and reveal the need for a deeper understanding of molecular mechanisms underlying allograft rejection.
ISSN
1557-3117
Published In/Presented At
Lee, D. H., Usmani, A., Ravichandran, V., Wicks, T., Wu, R., Wolf-Doty, T., Dumitru, I., Berman, P., Oliveira, G. H., & Mackie, B. (2023). Relationship Between Blood and Tissue-Based Rejection-Related Transcripts in Heart Transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, S1053-2498(23)02018-1. Advance online publication. https://doi.org/10.1016/j.healun.2023.09.009
Disciplines
Medical Education | Medicine and Health Sciences
PubMedID
37730189
Department(s)
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students
Document Type
Article