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

antibody-mediated rejection antibody-mediated rejection (AMR) lung transplantation mammalian target of rapamycin (mTOR) pathway phosphorylated s6 ribosomal protein (p-S6RP)

Journal

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703

Informations de publication

Date de publication:
06 Oct 2023
Historique:
received: 15 03 2023
revised: 27 09 2023
accepted: 02 10 2023
pubmed: 9 10 2023
medline: 9 10 2023
entrez: 8 10 2023
Statut: aheadofprint

Résumé

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. 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. 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%. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

DOI: 10.1016/j.healun.2023.10.002 PMID: 37806601
pubmed: 37806601
pii: S1053-2498(23)02062-4
doi: 10.1016/j.healun.2023.10.002
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Francesca Lunardi (F)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Luca Vedovelli (L)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Federica Pezzuto (F)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Jerome Le Pavec (J)

Service de Pneumologie et de Transplantation Pulmonaire, Groupe Hospitalier Marie-Lannelongue-Paris Saint Joseph, Le Plessis-Robinson, France; Faculty of Medicine, Université Paris-Saclay, Le Kremlin Bicêtre, France; UMR_S 999, Université Paris-Sud, INSERM, Groupe hospitalier Marie-Lannelongue-Saint Joseph, Le Plessis-Robinson, France.

Peter Dorfmuller (P)

UMR_S 999, Université Paris-Sud, INSERM, Groupe hospitalier Marie-Lannelongue-Saint Joseph, Le Plessis-Robinson, France.

Marina Ivanovic (M)

Department of Pathology, Loyola University Medical Center, Chicago, Illinois.

Tahuanty Pena (T)

Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa.

Katharina Wassilew (K)

Department of Pathology, Rigshospitalet, Copenhagen, Denmark.

Michael Perch (M)

Department of Cardiology, Section for Lung Transplantation, Righospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Sandrine Hirschi (S)

Department of Respiratory Medicine, University Hospital of Strasbourg, Strasbourg, France.

Marie-Pierre Chenard (MP)

Department of Pathology, University Hospital of Strasbourg, Strasbourg, France.

Rebecca A Sosa (RA)

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.

Martin Goddard (M)

Department of Histopathology, Papworth Hospital NHS Trust, Cambridge, UK.

Desley Neil (D)

Department of Histopathology, Queen Elizabeth Hospital, Birmingham, UK.

Angeles Montero-Fernandez (A)

Department of Histopathology, Manchester University Hospital NHS Foundation Trust, Manchester, UK.

Alexandra Rice (A)

Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.

Emanuele Cozzi (E)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Federico Rea (F)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Deborah J Levine (DJ)

Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, Texas.

Antoine Roux (A)

Department of Pneumology, Hôpital Foch, Suresnes, France and Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France.

Gregory A Fishbein (GA)

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.

Fiorella Calabrese (F)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy. Electronic address: fiorella.calabrese@unipd.it.

Classifications MeSH