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

Alessia Giarraputo; Guillaume Coutance; Olivier Aubert; Marny Fedrigo; Fariza Mezine; Dina Zielinski; Michael Mengel; Patrick Bruneval; Jean-Paul Duong van Huyen; Annalisa Angelini; Alexandre Loupy

doi:10.3389/ti.2023.11710

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

Transpl Int. 2023 Sep 4:36:11710. doi: 10.3389/ti.2023.11710. eCollection 2023.

Authors

Alessia Giarraputo^{1

2}, Guillaume Coutance^{1

3}, Olivier Aubert^{1

4}, Marny Fedrigo², Fariza Mezine¹, Dina Zielinski¹, Michael Mengel⁵, Patrick Bruneval¹, Jean-Paul Duong van Huyen^{1

6}, Annalisa Angelini², Alexandre Loupy^{1

4}

Affiliations

¹ Université Paris Cité, INSERM U970 PARCC, Paris Institute for Transplantation and Organ Regeneration, Paris, France.
² Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy.
³ Department of Cardiac and Thoracic Surgery, Cardiology Institute, Pitie Salpetriere Hospital, Assistance Publique-Hopitaux de Paris (AP-HP), Sorbonne University Medical School, Paris, France.
⁴ Department of Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
⁶ Pathology Department, Hôpital Necker, AP-HP and Université de Paris, Paris, France.

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.

Keywords: antibody-mediated rejection; gene expression; heart rejection; heart transplantation; molecular profiling; transcriptome.

MeSH terms

Allografts
Antibodies*
Biopsy
Consensus
Humans
Organ Transplantation*

Substances

Antibodies

Grants and funding

This study was funded by MSD-Avenir research grant “iTRANSPLANT: Artificial Intelligence for precision medicine in organ transplantation,” and by OrganX. AG and MF were supported by a grant from University of Padua, Department of Cardiac, Thoracic and Vascular Sciences and Public Health (BIRD 204045). GC received a grant from the ADICARE association (2021). OA received a grant from the Foundation Bettencourt Schueller.