Evidence map›Paper›PMID 40568656›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Utility of Plasma Cell-free Chromatin Immunoprecipitation to Detect Cardiac Allograft Rejection.

Moon Kyoo Jang, Oladele Oluwayiose, Neelam Redekar, Temesgen E Andargie, Woojin Park, Muhtadi Alnababteh, Tom Hill, Kellie Phipps, Hyesik Kong, Xin Tian and 6 more

2 registry-linked trialsAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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.

NCT01985412 completednot on this map

Genome Transplant Dynamics: Non-Invasive Sequencing-Based Diagnosis of Rejection

TypeobservationalSponsorStanford UniversityRan2010 to 2013Enrolled65ConditionsCardiac Transplant Rejection, Lung Transplant Rejection
NCT02423070 recruitingnot on this map

Genome Transplant Dynamics

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2015 to 2034Enrolled991ConditionsThoracic Organ Transplantation
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Moon Kyoo JangGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0002-1657-2877
Oladele OluwayioseIntegrated Data Sciences Section, Research Technologies Branch, NIAID, NIH, Bethesda, Maryland, USA.
Neelam RedekarIntegrated Data Sciences Section, Research Technologies Branch, NIAID, NIH, Bethesda, Maryland, USA.
Temesgen E AndargieGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0003-2888-1316
Woojin ParkGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0001-9982-0057
Muhtadi AlnababtehGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0001-8521-9260
Tom HillIntegrated Data Sciences Section, Research Technologies Branch, NIAID, NIH, Bethesda, Maryland, USA.
Kellie PhippsLaboratory of Applied Precision Omics, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD.
Hyesik KongGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0001-7540-2045
Xin TianOffice of Biostatistics Research, NHLBI, NIH, Bethesda, MD.ORCID 0000-0003-1896-2462
Helen I LuikartDepartment of Medicine, Stanford University, Stanford, CA.ORCID 0000-0002-9782-4449
Michael A SolomonCritical Care Medicine Department, National Institutes of Health Clinical Center and Cardiovascular Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-7400-6614
Palak ShahGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0001-8175-168X
Hannah A ValantineGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0002-2948-9503
Kiran KhushDepartment of Medicine, Stanford University, Stanford, CA.ORCID 0000-0001-9697-5926
Sean Agbor-EnohGenomic Research Alliance for Transplantation (GRAfT), NIH, Bethesda, MD.ORCID 0000-0002-9380-9161

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Antibody-mediated rejection (AMR) remains the major risk factor for allograft loss across all solid organ transplantation. Unfortunately, its diagnosis relies on biopsy, an invasive gold standard that often sample unaffected allograft tissue leading to missed diagnosis. Plasma donor-derived cell-free DNA (dd-cfDNA) is noninvasive biomarker that has high sensitivity but low specificity for AMR diagnosis. This proof-of-concept study assessed the utility of cell-free chromatin immunoprecipitation (cfChIP) as a surrogate for gene expression to detect cardiac AMR and the associated pathobiology. Methods: The discovery GRAfT multicenter cohort of heart transplant patients (NCT02423070) identified AMR, acute cellular rejection (ACR), and stable controls based on biopsy and ddcfDNA results. Plasma cfChIP-sequencing was performed to identify peaks, associated genes and pathobiological pathways. Plasma from an external cohort (GTD, NCT01985412) was also analyzed to verify pathways identified. Digital droplet PCR (ddPCR) assays targeting differential regions were constructed to test the diagnostic performance of cfDNA to detect AMR/ACR from stable controls (rejection-specific assays) or AMR from ACR (AMR-specific assays). Results: The cohort included 21 AMR, 28 ACR, and 45 stable controls from GRAfT and GTD, and 23 healthy controls. cfChIP detected expected active genes, including housekeeping genes and gene targets of transplant immunosuppressive drugs but not inactive genes. Unsupervised clustering of the discovery GRAfT cohort assigned 95% of samples correctly as AMR, ACR or stable control. Differential analysis identified pathobiological pathways of AMR such as neutrophil degranulation and complement activation. The pathways were consistent in GTD samples. Rejection-specific assays detected AMR/ACR from controls with AUC of 0.78 - 0.95. AMR-specific assays detected AMR from ACR with AUC of 0.71 - 0.85, sensitivities of 0.73 - 0.94 and specificities of 0.73 - 0.80. Conclusion: This study provides valuable preliminary data supporting the use of cfChIP to detect AMR and the associated pathobiological pathways.

Indexed as

Allograft rejectionAntibody mediated rejection (AMR)cfChIPHeart transplantationLiquid biopsy

Identifiers

PMID40568656
PMCPMC12191110

What OpenQuestion holds

Textmetadata
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.