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Article Dans Une Revue The Journal of Heart and Lung Transplantation Année : 2024

Assessing the role of phosphorylated S6 ribosomal protein in the pathological diagnosis of pulmonary antibody-mediated rejection

Francesca Lunardi
Luca Vedovelli
Federica Pezzuto
Marina Ivanovic
  • Fonction : Auteur
Tahuanty Pena
Katharina Wassilew
  • Fonction : Auteur
Michael Perch
Sandrine Hirschi
Marie-Pierre Chenard
Rebecca Sosa
  • Fonction : Auteur
Martin Goddard
  • Fonction : Auteur
Desley Neil
Angeles Montero-Fernandez
Alexandra Rice
  • Fonction : Auteur
Emanuele Cozzi
  • Fonction : Auteur
Federico Rea
  • Fonction : Auteur
Deborah Levine
  • Fonction : Auteur
Gregory Fishbein
  • Fonction : Auteur
Fiorella Calabrese

Résumé

Background: Pulmonary antibody-mediated rejection is still a challenging diagnosis as C4d immunostaining has poor sensitivity. Previous studies have indicated that the phosphorylated S6 ribosomal protein, a component of the mammalian target of rapamycin (mTOR) pathway, is correlated with de novo donor-specific antibodies in lung transplantation. The objective of this study was to evaluate the phosphorylation of S6 ribosomal protein as a surrogate for antibody-mediated rejection diagnosis in lung transplant patients. Methods: This multicentre retrospective study analyzed transbronchial biopsies from 216 lung transplanted patients, 114 with antibody-mediated rejection and 102 without (19 with acute cellular rejection, 17 with ischemia/reperfusion injury, 18 with infection, and 48 without post-transplant complications). Immunohistochemistry was used to quantify phosphorylated S6 ribosomal protein expression in macrophages, endothelium, epithelium, and inter-pathologist agreement was assessed. Results: Median phosphorylated S6 ribosomal protein expression values were higher in antibody-mediated rejection cases than in controls for all cell components, with the highest sensitivity in macrophages (0.9) and the highest specificity in endothelial expression (0.8). The difference was mainly significant in macrophages compared to other post-lung transplantation complications. Inter-pathologist agreement was moderate for macrophages and endothelium, with higher agreement when phosphorylated S6 ribosomal protein expression was dichotomized into positive/negative. The inclusion of phosphorylated S6 ribosomal protein in the diagnostic algorithm could have increased antibody-mediated rejection certainty levels by 25%. Conclusions: The study supports the role of the mTOR pathway in antibody-mediated rejection-related graft injury and suggests that tissue phosphorylation of S6 ribosomal protein could be a useful surrogate for a more accurate pathological diagnosis of lung antibody-mediated rejection.

Dates et versions

hal-04481951 , version 1 (28-02-2024)

Identifiants

Citer

Francesca Lunardi, Luca Vedovelli, Federica Pezzuto, Jerome Le Pavec, Peter Dorfmuller, et al.. Assessing the role of phosphorylated S6 ribosomal protein in the pathological diagnosis of pulmonary antibody-mediated rejection. The Journal of Heart and Lung Transplantation, 2024, 43 (3), pp.403-413. ⟨10.1016/j.healun.2023.10.002⟩. ⟨hal-04481951⟩
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