Banff Human Organ Transplant Consensus Gene Panel for the Detection of Antibody Mediated Rejection in Heart Allograft Biopsies.

Abstract

The molecular refinement of the diagnosis of heart allograft rejection based on whole-transcriptome analyses faces several hurdles that greatly limit its widespread clinical application. The targeted Banff Human Organ Transplant gene panel (B-HOT, including 770 genes of interest) has been developed to facilitate reproducible and cost-effective gene expression analysis of solid organ allografts. We aimed to determine in silico the ability of this targeted panel to capture the antibody-mediated rejection (AMR) molecular profile using whole-transcriptome data from 137 heart allograft biopsies (71 biopsies reflecting the entire landscape of histologic AMR, 66 non-AMR control biopsies including cellular rejection and non-rejection cases). Differential gene expression, pathway and network analyses demonstrated that the B-HOT panel captured biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cell-related genes), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions, endothelial activation) and networks reflecting the pathophysiological mechanisms underlying the AMR process previously identified in whole-transcriptome analysis. Our findings support the potential clinical use of the B-HOT-gene panel as a reliable proxy to whole-transcriptome analysis for the gene expression profiling of cardiac allograft rejection.