Banff Human Organ Transplant consensus gene panel for detecting antibody mediated rejection in heart allograft biopsies.

Tissue-based gene expression approaches have been developed as a companion tool of routine pathology to refine the diagnosis of cardiac rejection. Whole-transcriptome profiling was used to define molecular phenotypes of rejection but its clinical application remains limited by several hurdles. The Banff Human Organ Transplant (BHOT) panel is a consensus list of 770 genes developed to facilitate cost-effective and reproducible expression analysis of solid organ allografts. We aimed at validating in-silico the targeted panel as a proxy to whole-transcriptome analysis. To assess the BHOT panel reliability in detecting gene expression pattern associated with antibody-mediated rejection (AMR), we performed in silico analysis and projected the BHOT panel on already published microarray data of 141 heart transplant biopsies We compared the targeted and whole-transcriptome molecular profiles in AMR-biopsies (n = 71) and non-AMR matched-control (non-rejection or acute cellular rejection, n = 71) by performing differential expression, pathway, and network analyses. Out of the 30 most differentially expressed genes between AMR and non-AMR identified in whole-transcriptome analysis, two-thirds (n = 19) were included in the BHOT panel (Figure 1). These genes covered major immune pathways and key cells involved in the physiology of AMR. Overall, differential gene expression, pathway and network analyses showed that the targeted gene expression analysis was able to detect biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cells), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions) and networks reflecting the pathophysiological mechanisms associated with AMR previously identified in whole-transcriptome analysis. The targeted molecular signature of AMR based on the B-HOT panel detected relevant AMR-related genes and pathways. The targeted panel can be used as a proxy to whole-transcriptome to analyze the molecular profile of heart allograft rejection. [ABSTRACT FROM AUTHOR]