Journal article
ASSESSING THE ROLE OF PHOSPHORYLATED S6 RIBOSOMAL PROTEIN IN THE PATHOLOGICAL DIAGNOSIS OF PULMONARY ANTIBODY-MEDIATED REJECTION
The Journal of heart and lung transplantation, Vol.43(3), pp.403-413
03/2024
DOI: 10.1016/j.healun.2023.10.002
PMID: 37806601
Abstract
Pulmonary antibody-mediated rejection is still a challenging diagnosis as C4d 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 AMR 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.
Details
- Title: Subtitle
- ASSESSING THE ROLE OF PHOSPHORYLATED S6 RIBOSOMAL PROTEIN IN THE PATHOLOGICAL DIAGNOSIS OF PULMONARY ANTIBODY-MEDIATED REJECTION
- Creators
- Francesca Lunardi - University of PaduaLuca Vedovelli - University of PaduaFederica Pezzuto - University of PaduaJerome Le Pavec - Hôpital Marie LannelonguePeter Dorfmuller - Hôpital Marie LannelongueMarina Ivanovic - Loyola University Medical CenterTahuanty Pena - University of IowaKatharina Wassilew - RigshospitaletMichael Perch - RigshospitaletSandrine Hirschi - Université de StrasbourgMarie-Pierre Chenard - Department of Pathology, University Hospital of Strasbourg, Strasbourg, FranceRebecca A. Sosa - University of California, Los AngelesMartin Goddard - Papworth HospitalDesley Neil - Queen Elizabeth Hospital BirminghamAngeles Montero-Fernandez - Manchester University NHS Foundation TrustAlexandra Rice - Royal Brompton & Harefield NHS Foundation TrustEmanuele Cozzi - University of PaduaFederico Rea - University of PaduaDeborah J Levine - The University of Texas Health Science Center at San AntonioAntoine Roux - Hôpital FochGregory A. Fishbein - University of California, Los AngelesFiorella Calabrese - University of Padua
- Resource Type
- Journal article
- Publication Details
- The Journal of heart and lung transplantation, Vol.43(3), pp.403-413
- DOI
- 10.1016/j.healun.2023.10.002
- PMID
- 37806601
- NLM abbreviation
- J Heart Lung Transplant
- ISSN
- 1053-2498
- eISSN
- 1557-3117
- Publisher
- Elsevier Inc
- Language
- English
- Electronic publication date
- 10/06/2023
- Date published
- 03/2024
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984476433902771
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