Organizing pneumonia is associated with molecular allograft injury and the development of antibody-mediated rejection.

Humans Prospective Studies Transplantation, Homologous Antibodies Pneumonia Allografts Cell-Free Nucleic Acids Organizing Pneumonia Graft Rejection / diagnosis
acute rejection antibody-mediated rejection donor-derived cell-free DNA molecular allograft injury organizing pneumonia

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:
Apr 2024
Historique:
received: 24 07 2023
revised: 28 10 2023
accepted: 08 11 2023
medline: 18 3 2024
pubmed: 17 11 2023
entrez: 16 11 2023
Statut: ppublish

Résumé

The association between organizing pneumonia (OP) after lung transplantation with the development of acute rejection (AR) remains undefined. In addition, molecular allograft injury, as measured by donor-derived cell-free DNA (dd-cfDNA), during episodes of OP and its relationship to episodes of AR, chronic lung allograft dysfunction (CLAD), or death is unknown. This multicenter, prospective cohort study collected serial plasma samples from 188 lung transplant recipients for dd-cfDNA at the time of bronchoscopy with biopsy. Multivariable Cox regression was used to analyze the association between OP with the development of AR (antibody-mediated rejection (AMR) and acute cellular rejection (ACR)), CLAD, and death. Multivariable models were performed to test the association of dd-cfDNA at OP with the risk of AR, CLAD, or death. In multivariable analysis, OP was associated with increased risk of AMR (hazard ratio (HR) = 2.26, 95% confidence interval (CI) 1.04-4.92, p = 0.040) but not ACR (HR = 1.29, 95% CI: 0.66-2.5, p = 0.45) or the composite outcome of CLAD or death (HR = 0.88, 95% CI, 0.47-1.65, p = 0.69). Median levels of dd-cfDNA were higher in OP compared to stable controls (1.33% vs 0.43%, p = 0.0006). Multivariable analysis demonstrated that levels of dd-cfDNA at diagnosis of OP were associated with increased risk of both AMR (HR = 1.29, 95% CI 1.03-1.62, p = 0.030) and death (HR = 1.16, 95% CI, 1.02-1.31, p = 0.026). OP is independently associated with an increased risk of AMR but not CLAD or death. The degree of molecular allograft injury at the diagnosis of OP may further predict the risk of AMR and death.

Sections du résumé

BACKGROUND BACKGROUND
The association between organizing pneumonia (OP) after lung transplantation with the development of acute rejection (AR) remains undefined. In addition, molecular allograft injury, as measured by donor-derived cell-free DNA (dd-cfDNA), during episodes of OP and its relationship to episodes of AR, chronic lung allograft dysfunction (CLAD), or death is unknown.
METHODS METHODS
This multicenter, prospective cohort study collected serial plasma samples from 188 lung transplant recipients for dd-cfDNA at the time of bronchoscopy with biopsy. Multivariable Cox regression was used to analyze the association between OP with the development of AR (antibody-mediated rejection (AMR) and acute cellular rejection (ACR)), CLAD, and death. Multivariable models were performed to test the association of dd-cfDNA at OP with the risk of AR, CLAD, or death.
RESULTS RESULTS
In multivariable analysis, OP was associated with increased risk of AMR (hazard ratio (HR) = 2.26, 95% confidence interval (CI) 1.04-4.92, p = 0.040) but not ACR (HR = 1.29, 95% CI: 0.66-2.5, p = 0.45) or the composite outcome of CLAD or death (HR = 0.88, 95% CI, 0.47-1.65, p = 0.69). Median levels of dd-cfDNA were higher in OP compared to stable controls (1.33% vs 0.43%, p = 0.0006). Multivariable analysis demonstrated that levels of dd-cfDNA at diagnosis of OP were associated with increased risk of both AMR (HR = 1.29, 95% CI 1.03-1.62, p = 0.030) and death (HR = 1.16, 95% CI, 1.02-1.31, p = 0.026).
CONCLUSIONS CONCLUSIONS
OP is independently associated with an increased risk of AMR but not CLAD or death. The degree of molecular allograft injury at the diagnosis of OP may further predict the risk of AMR and death.

Identifiants

DOI: 10.1016/j.healun.2023.11.008 PMID: 37972825
pubmed: 37972825
pii: S1053-2498(23)02125-3
doi: 10.1016/j.healun.2023.11.008
pii:
doi:

Substances chimiques

Antibodies 0
Cell-Free Nucleic Acids 0

Types de publication

Multicenter Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

563-570

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Auteurs

Michael B Keller (MB)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland.

Xin Tian (X)

Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Moon Kyoo Jang (MK)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Rohan Meda (R)

Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Ananth Charya (A)

University of Maryland Medical Center, Baltimore, Maryland.

Deniz Ozisik (D)

Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Gerald J Berry (GJ)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Stanford University School of Medicine, Stanford, California.

Charles C Marboe (CC)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons of Columbia University, New York, New York.

Hyesik Kong (H)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Ileana L Ponor (IL)

Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.

Shambhu Aryal (S)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Fairfax, Virginia.

Jonathan B Orens (JB)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland.

Pali D Shah (PD)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland.

Steven D Nathan (SD)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Fairfax, Virginia.

Sean Agbor-Enoh (S)

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: sean.agbor-enoh@nih.gov.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Organizing pneumonia is associated with...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Organizing pneumonia is associated with...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation homologue › Organizing pneumonia is associated with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Organizing pneumonia is associated with...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Organizing pneumonia is associated with...
questionsmedicales.fr › Régions du corps › Transplants › Allogreffes › Organizing pneumonia is associated with...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › Acides nucléiques acellulaires › Organizing pneumonia is associated with...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Maladies pulmonaires › Bronchopneumopathies obstructives › Bronchiolite oblitérante › Pneumonie organisée › Organizing pneumonia is associated with...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunologie en transplantation › Réaction de l'hôte contre le greffon › Rejet du greffon › Organizing pneumonia is associated with...