Evidence map›Paper›PMID 40120999›Full record

Observational studyThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2025

Molecular criteria for pulmonary antibody-mediated rejection are associated with an increased risk of allograft failure.

Michael B Keller, David Newman, Muhtadi Alnababteh, Ann Bon, Lucia Ponor, Pali Shah, Joby Mathew, Hyesik Kong, Temesgen Andargie, Woojin Park and 9 more

Registry-linked trialAbstract readObservational StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07516379 (GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT07516379 recruitingnot on this mapstarted 2026, after this paper: background citation

GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2026 to 2032Enrolled100ConditionsLung Transplant, End Stage Lung Disease, Rejection
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  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. 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
  3. 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
  4. Article
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

19 authors.

Michael B KellerDivision of Pulmonary, Critical Care & Sleep Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Laborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
David NewmanCollege of Nursing, Florida Atlantic University, Boca Raton, Florida.
Muhtadi AlnababtehLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Ann BonLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
Lucia PonorGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Division of Hospital Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
Pali ShahGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
Joby MathewGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
Hyesik KongLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
Temesgen AndargieLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
Woojin ParkLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
Ananth CharyaDivision of Pulmonary, Critical Care & Sleep Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
Helen LuikartDivision of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California; Department of Pathology, Stanford University School of Medicine, Palo Alto, California.
Tyler IntrieriDivision of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California; Department of Pathology, Stanford University School of Medicine, Palo Alto, California.
Shambhu AryalGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Pulmonary Division, Inova Fairfax Hospital, Falls Church, Virginia.
Steven D NathanGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Pulmonary Division, Inova Fairfax Hospital, Falls Church, Virginia.
Jonathan B OrensGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
Kiran K KhushDivision of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California.
Moon JangLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
Sean Agbor-EnohLaborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address: sean.agbor-enoh@nih.gov.

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 HL999999Intramural NIH HHS ZIA HL006268
6 · The paper itself

Abstract

backgroundCurrent International Society for Heart and Lung Transplantation (ISHLT) criteria for pulmonary antibody-mediated rejection (AMR) is predicated on a constellation of clinical, laboratory and histopathological parameters, including the presence of donor-specific antibodies (DSA). However, molecular evidence of allograft injury is not considered. The aim of this study was to investigate if allograft injury on the molecular level, as measured by donor-derived cell-free DNA (dd-cfDNA), identifies DSA positive patients experiencing a form of AMR associated with increased risk of chronic lung allograft dysfunction (CLAD) or death.

methodsThis multicenter, observational analysis included adult lung transplant recipients from 2 prospective cohort studies. Serial plasma samples were collected for dd-cfDNA measurement by shotgun sequencing. Molecular AMR was defined as the presence of DSA and dd-cfDNA level >1% occurring >30 days post-transplant. Clinical AMR was defined using ISHLT criteria. Time-dependent multivariable Cox regression models were used to determine the association of Clinical AMR or Molecular AMR with the composite outcome of CLAD or death.

resultsThe final analysis included 209 subjects. Sixty-one subjects met criteria for molecular AMR. Molecular AMR captured 42/46 (91%) of patients who experienced Clinical AMR. Molecular AMR was associated with an increased risk of CLAD or death (HR 2.00, 95% CI: 1.18-3.38, p = 0.010). The results remained consistent analyzing Molecular AMR subjects without concomitant ISHLT Clinical AMR, acute rejection, or infection (HR 2.45, 95% CI: 1.01-5.94, p = 0.047).

conclusionsMolecular AMR identifies a population of lung transplant recipients potentially experiencing antibody-mediated rejection not captured by current ISHLT criteria.

Indexed as

Graft RejectionIsoantibodiesLung TransplantationAdultAllograftsCell-Free Nucleic AcidsFemaleHumansMaleMiddle AgedProspective StudiesRisk FactorsCell-Free Nucleic AcidsIsoantibodiesAcute RejectionAntibody Mediated RejectionDonor Specific AntibodiesLung TransplantationMolecular Allograft Injury

Identifiers

PMID40120999
PMCPMC12353349

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.