Ultrastructural changes in pulmonary allografts with antibody-mediated rejection.
antibody-mediated rejection
donor-specific antibodies
endothelium
lung allograft
ultrastructural features
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:
02 2020
02 2020
Historique:
received:
15
02
2019
revised:
02
10
2019
accepted:
27
11
2019
pubmed:
25
12
2019
medline:
1
4
2021
entrez:
25
12
2019
Statut:
ppublish
Résumé
Antibody-mediated rejection (AMR) is an important cause of lung allograft loss in some patients. Challenges with current diagnostic criteria limit timely detection. Ultrastructural studies of endothelia allow the early detection of AMR in kidney allografts. This study aimed to define the ultrastructural changes of the endothelium in lung allografts in the setting of AMR and determine its specificity for AMR. Ultrastuctural studies were performed on lung allograft biopsies of 12 patients using glutaraldehyde-fixed or paraffin-embedded material. AMR had been classified according to the International Society of Heart and Lung Transplant 2016 consensus report criteria. Endothelial changes (swelling [ES], vacuolization [EV], surface irregularity, detachment, neutrophil margination [NM]) and basement membrane changes were graded semi quantitatively using electron microscopy (EM). Grades were compared between AMR, acute cellular rejection, and non-transplant controls. Significant differences were found between AMR and acute cellular reaction biopsies, particularly in ES (p = 0.006), EV (p = 0.023) and NM (p = 0.038). Using a combined score of all categories of assessment, the total EM score was significantly higher in AMR (p = 0.007) and provided excellent sensitivity and specificity with a receiver operator characteristic curve of 1.0. C4d did not correlate with EM changes associated with AMR. The use of paraffin-embedded material samples did not significantly affect the analysis compared with glutaraldehyde-fixed tissue, although ES was reduced in the former. Endothelial structural analysis using EM can facilitate improved diagnostic accuracy of AMR and needs to be validated in larger cohorts, but it also allows retrospective studies to be performed.
Sections du résumé
BACKGROUND
Antibody-mediated rejection (AMR) is an important cause of lung allograft loss in some patients. Challenges with current diagnostic criteria limit timely detection. Ultrastructural studies of endothelia allow the early detection of AMR in kidney allografts. This study aimed to define the ultrastructural changes of the endothelium in lung allografts in the setting of AMR and determine its specificity for AMR.
METHODS
Ultrastuctural studies were performed on lung allograft biopsies of 12 patients using glutaraldehyde-fixed or paraffin-embedded material. AMR had been classified according to the International Society of Heart and Lung Transplant 2016 consensus report criteria. Endothelial changes (swelling [ES], vacuolization [EV], surface irregularity, detachment, neutrophil margination [NM]) and basement membrane changes were graded semi quantitatively using electron microscopy (EM). Grades were compared between AMR, acute cellular rejection, and non-transplant controls.
RESULTS
Significant differences were found between AMR and acute cellular reaction biopsies, particularly in ES (p = 0.006), EV (p = 0.023) and NM (p = 0.038). Using a combined score of all categories of assessment, the total EM score was significantly higher in AMR (p = 0.007) and provided excellent sensitivity and specificity with a receiver operator characteristic curve of 1.0. C4d did not correlate with EM changes associated with AMR. The use of paraffin-embedded material samples did not significantly affect the analysis compared with glutaraldehyde-fixed tissue, although ES was reduced in the former.
CONCLUSIONS
Endothelial structural analysis using EM can facilitate improved diagnostic accuracy of AMR and needs to be validated in larger cohorts, but it also allows retrospective studies to be performed.
Identifiants
pubmed: 31870771
pii: S1053-2498(19)31793-0
doi: 10.1016/j.healun.2019.11.022
pii:
doi:
Substances chimiques
HLA Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
165-175Informations de copyright
Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.