Donor-derived, cell-free DNA levels by next-generation targeted sequencing are elevated in allograft rejection after lung transplantation.
Journal
ERJ open research
ISSN: 2312-0541
Titre abrégé: ERJ Open Res
Pays: England
ID NLM: 101671641
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
04
07
2020
accepted:
18
09
2020
entrez:
3
2
2021
pubmed:
4
2
2021
medline:
4
2
2021
Statut:
epublish
Résumé
Surveillance after lung transplantation is critical to the detection of acute cellular rejection (ACR) and prevention of chronic lung allograft dysfunction (CLAD). Therefore, we measured donor-derived cell-free DNA (dd-cfDNA) implementing a clinical-grade, next-generation targeted sequencing assay in 107 plasma samples from 38 unique lung transplantation recipients with diagnostic cohorts classified as: (1) biopsy-confirmed or treated ACR, (2) antibody-mediated rejection (AMR), (3) obstructive CLAD, (4) allograft infection (INFXN) and (5) Stable healthy allografts (STABLE). Our principal findings are as follows: (1) dd-cfDNA level was elevated in ACR (median 0.91%; interquartile range (IQR): 0.39-2.07%), CLAD (2.06%; IQR: 0.57-3.67%) and an aggregated cohort of rejection encompassing allograft injury (1.06%; IQR: 0.38-2.51%), compared with the STABLE cohort (0.38%; IQR: 0.23-0.87%) (p=0.02); (2) dd-cfDNA level with AMR was elevated (1.34%; IQR: 0.34-2.40%) compared to STABLE, although it did not reach statistical significance (p=0.07) due to limitations in sample size; (3) there was no difference in dd-cfDNA for allograft INFXN (0.39%; IQR: 0.18-0.67%)
Identifiants
pubmed: 33532456
doi: 10.1183/23120541.00462-2020
pii: 00462-2020
pmc: PMC7836440
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL095686
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141105
Pays : United States
Informations de copyright
Copyright ©ERS 2021.
Déclaration de conflit d'intérêts
Conflict of interest: K.K. Khush reports grants and personal fees from CareDx, Inc., outside the submitted work. Conflict of interest: I. De Vlaminck has nothing to disclose. Conflict of interest: H. Luikart has nothing to disclose. Conflict of interest: D.J. Ross has nothing to disclose. Conflict of interest: M.R. Nicolls has nothing to disclose.
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