Evidence map›Paper›PMID 34130911›Full record

ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2021

Donor-derived cell-free DNA accurately detects acute rejection in lung transplant patients, a multicenter cohort study.

Moon Kyoo Jang, Ilker Tunc, Gerald J Berry, Charles Marboe, Hyesik Kong, Michael B Keller, Pali D Shah, Irina Timofte, Anne W Brown, Ileana L Ponor and 7 more

Open access · greenAbstract readMulticenter Study
In one paragraph

Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 2 pooled it
11.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. International Society for Heart and Lung Transplantation Scientific Statement on pulmonary antibody-mediated rejection and proposed graft, antibody, and pathology (GAP) definition.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Guideline
  2. Pooled it
  3. Article
  4. Utility of donor-derived cell-free DNA testing after lung transplantation in the precision medicine era.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Review
  5. Article
  6. Article
  7. Donor-derived cell-free DNA associated with increased risk of chronic lung allograft dysfunction and mortality: Are absolute levels better than percentage?The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Observational
  8. Exploring acute cellular rejection in lung transplantation: insights from donor-derived cell-free DNA analysis.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2026
    Article
  9. Exploring acute cellular rejection in lung transplantation: insights from donor-derived cell-free DNA analysis.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Molecular criteria for pulmonary antibody-mediated rejection are associated with an increased risk of allograft failure.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
    Observational
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 9 institutions in 1 country.

Moon Kyoo JangGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland.
Ilker TuncDivision of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland.
Gerald J BerryGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Stanford University School of Medicine, Palo Alto, California.
Charles MarboeGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Department of Pathology, New York Presbyterian University Hospital of Cornell and Columbia, New York, New York.
Hyesik KongGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland.
Michael B KellerGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 1830 East Monument Street, Baltimore, Maryland.
Pali D ShahGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 1830 East Monument Street, Baltimore, Maryland.
Irina TimofteGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; University of Maryland Medical Center, Baltimore, Maryland.
Anne W BrownGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Inova Fairfax Hospital, Fairfax, Virginia.
Ileana L PonorDepartment of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
Cedric MutebiImmunogenetics Core Laboratory, Johns Hopkins Hospital, Baltimore, Maryland.
Mary C PhilogeneGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; National Cancer Institute, Rockville, Maryland.
Kai YuNational Cancer Institute, Rockville, Maryland.
Aldo IaconoGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; University of Maryland Medical Center, Baltimore, Maryland.
Jonathan B OrensGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Stanford University School of Medicine, Palo Alto, California.
Steven D NathanGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Inova Fairfax Hospital, Fairfax, Virginia.
Sean Agbor-EnohGenomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 1830 East Monument Street, Baltimore, Maryland. Electronic address: sean.agbor-enoh@nih.gov.
National Heart Lung and Blood Institute · USInova Fairfax Hospital · USJohns Hopkins University · USNational Cancer Institute · USPalo Alto University · USUniversity of Maryland Medical Center · USCornell University · USJohns Hopkins Bayview Medical Center · USJohns Hopkins Hospital · US

Funding

Cell-free DNA to detect transplant rejectionZIAHL006268 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI AGBOR-ENOH, SEAN · 2021 to 2025
$8.8M
Intramural NIH HHS Z99 HL999999
6 · The paper itself

Abstract

backgroundAcute rejection, which includes antibody-mediated rejection and acute cellular rejection, is a risk factor for lung allograft loss. Lung transplant patients often undergo surveillance transbronchial biopsies to detect and treat acute rejection before irreversible chronic rejection develops. Limitations of this approach include its invasiveness and high interobserver variability. We tested the performance of percent donor-derived cell-free DNA (%ddcfDNA), a non-invasive blood test, to detect acute rejection.

methodsThis multicenter cohort study monitored 148 lung transplant subjects over a median of 19.6 months. We collected serial plasma samples contemporaneously with TBBx to measure %ddcfDNA. Clinical data was collected to adjudicate for acute rejection. The primary analysis consisted of computing the area-under-the-receiver-operating-characteristic-curve of %ddcfDNA to detect acute rejection. Secondary analysis determined %ddcfDNA rule-out thresholds for acute rejection.

resultsddcfDNA levels were high after transplant surgery and decayed logarithmically. With acute rejection, ddcfDNA levels rose six-fold higher than controls. ddcfDNA levels also correlated with severity of lung function decline and histological grading of rejection. %ddcfDNA area-under-the-receiver-operating-characteristic-curve for acute rejection, AMR, and ACR were 0.89, 0.93, and 0.83, respectively. ddcfDNA levels of <0.5% and <1.0% showed a negative predictive value of 96% and 90% for acute rejection, respectively. Histopathology detected one-third of episodes with ddcfDNA levels ≥1.0%, even though >90% of these events were coincident to clinical complications missed by histopathology.

conclusionsThis study demonstrates that %ddcfDNA reliably detects acute rejection and other clinical complications potentially missed by histopathology, lending support to its use as a non-invasive marker of allograft injury.

Indexed as

Acute DiseaseAdolescentAdultAgedBiomarkersBiopsyCell-Free Nucleic AcidsFemaleGraft RejectionHumansLung TransplantationMaleMiddle AgedROC CurveTransplantation, HomologousYoung AdultBiomarkersCell-Free Nucleic Acidscell-free DNAearly diagnosisrejection

Identifiers

PMID34130911
PMCPMC8319066
OpenAlexW3158127383

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.