Article Dans Une Revue American Journal of Transplantation Année : 2025

Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant gene panel: a multicenter international study

Viviane Gnemmi
Michelle Elias
Kevin Louis
Ivy A Rosales
Benjamin Adam
Robert B Colvin
Michael Mengel

Résumé

Transcriptomic analysis of kidney biopsies has demonstrated the potential to improve diagnosis of allograft rejection. Here, we developed a molecular assessment of antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR) based on the Banff Human Organ Transplant consensus gene panel. Expression assays of formalin-fixed paraffin-embedded kidney biopsies from well-phenotyped cohorts were used to develop prediction models for AMR and TCMR and an automated report of gene expression-based diagnosis. The study population consisted of 950 kidney allograft biopsies from 10 transplantation centers in Europe and North America. The development cohort included 664 renal allograft biopsies split into a training (n = 537) and test set (n = 127), and 2 external validation cohorts (n = 286). We performed gene selection using regularized regression and developed several different base models based on Banff Human Organ Transplant expression data, which were combined into a single ensemble model for each rejection diagnosis. Model performance was assessed in the test set and the 2 external validation cohorts, showing good discriminative abilities (respective areas under the precision-recall curve: AMR = 0.811, 0.891, and 0.832 and TCMR = 0.736, 0.810, and 0.782). We identified challenging biopsies with histology below diagnostic thresholds for which gene expression-based probability can refine rejection diagnosis. This automated molecular diagnostic system shows potential for improving kidney allograft rejection diagnosis in routine practice and clinical trials.

Fichier principal
Vignette du fichier
main.pdf (1.54 Mo) Télécharger le fichier
1-s2.0-S1600613525002308-mmc1.pdf (1.1 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
Licence

Dates et versions

hal-05103132 , version 1 (08-06-2025)

Licence

Identifiants

Citer

Dina Zielinski, Valentin Goutaudier, Marta Sablik, Gillian Divard, Olivier Aubert, et al.. Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant gene panel: a multicenter international study. American Journal of Transplantation, In press, ⟨10.1016/j.ajt.2025.04.025⟩. ⟨hal-05103132⟩

Collections

142 Consultations
393 Téléchargements

Altmetric

Partager

  • More