Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using a network approach to define relationships among tests for kidney transplant antibody-mediated rejection in a cross-sectional study.

ABSTRACT: Effective therapies for kidney transplant antibody-mediated rejection (ABMR) (Mayer et al, 2024) will require accurate diagnoses plus assessment of ABMR activity, and the new tests that were used to show treatment effects in the clinical trial such as donor-derived cell-free DNA (dd-cfDNA) and molecular biopsy analysis (MMDx) could be useful. ). In a partial correlation network, all four tests were correlated, in a hierarchy of inter-test correlations: MMDx ABMR > dd-cfDNA > histology ABMR > and DSA. Surprisingly, DSA correlated at least as strongly with MMDx ABMR as with histologic ABMR, even though DSA is not used in MMDx. When expressed in the same six rejection classes, MMDx diagnosed ABMR more frequently than histology. When histology disagreed with MMDx ABMR, dd-cfDNA, and DSA correlated more strongly with MMDx assessment. However, histology also detected ABMR lesions in some cases that MMDx called no rejection, correlating with subthreshold molecular ABMR activity and dd-cfDNA and DSA (AJT 25:72-87, 2024). Thus, the four-way inter-test correlations extend below current thresholds for diagnosing ABMR. Molecular rejection predicted outcomes better than histologic rejection in Trifecta, confirmed in the earlier INTERCOMEX study. These results map a network of four ABMR-related tests that can add precision to ABMR assessment in trials and clinical management and highlight the need to establish the clinical significance of subthreshold ABMR activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288273 | GEO | 2025/07/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptomic signatures of antibody mediated rejection in early biopsies with negative histology in HLA incompatible kidney transplantation [RNA-seq]

Project description:Presensitized patients with circulating donor-specific antibodies (DSA) prior to transplantation are at risk for antibody-mediated rejection (ABMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold ABMR activity undetected by histology could be operating in some early biopsies.

2024-12-26 | GSE276593 | GEO

Transcriptomic signatures of antibody mediated rejection in early biopsies with negative histology in HLA incompatible kidney transplantation

2024-12-26 | GSE276194 | GEO

The Trifecta study: comparing plasma donor-derived cell-free DNA levels with the molecular phenotype of kidney transplant biopsies

Project description:Background. The Trifecta study (ClinicalTrials.gov #NCT04239703) is a prospective investigator-initiated trial to evaluate the relationship between plasma %dd-cfDNA at the time of indication biopsy and the molecular phenotype of the biopsy. Results. Median time of biopsy post-transplant was 455 days (5 days - 32 years), with case-mix similar to previous studies: 180 (60%) no rejection, 89 (30%) antibody-mediated rejection (ABMR), and 31 (10%) T cell-mediated rejection (TCMR) and mixed. In genome-wide mRNA measurements, all 20 top probesets correlating with %dd-cfDNA were previously annotated for association with ABMR and all rejection, either NK cell-expressed (e.g. GNLY, CCL4, TRDC, and S1PR5) or IFNG-inducible (e.g. PLA1A, IDO1, CXCL11, and WARS). Among gene set and classifier scores, %dd-cfDNA correlated very strongly with ABMR and all rejection, reasonably strongly with active TCMR, and weakly with inactive TCMR, kidney injury and atrophy-fibrosis. %dd-cfDNA was highest in active ABMR, mixed, and active TCMR but lower in late-stage ABMR and less active TCMR. By multivariate random forests and logistic regression, molecular rejection variables predicted %dd-cfDNA better than histologic variables. Conclusions. %dd-cfDNA at time of indication biopsy strongly correlates with active molecular rejection and has potential to reduce unnecessary biopsies.

2021-12-23 | GSE192444 | GEO

Transcriptomic profiling of blood memory B cell subsets in kidney transplant recipients

Project description:We compared the transcriptomic profile between patients without donor-specific antibodies (DSA-), patients with donor-specific antibodies without antibody-mediated rejection (DSA+ ABMR-) and patients with donor-specific antibodies and antibody-mediated rejection (DSA+ ABMR+). We found that patients with DSA+ ABMR+ had a distinct transcriptomic profile compared to DSA- and DSA+ ABMR- patients, characterized by upregulation of genes related to B cell activation and B cell effector functions.

2021-07-14 | GSE155670 | GEO

Comparing plasma donor-derived cell-free DNA to gene expression in endomyocardial biopsies in the Trifecta-Heart study.

Project description:Background. Plasma donor-derived cell-free DNA (dd-cfDNA) is used to screen for rejection in heart transplants. We launched the Trifecta-Heart (ClinicalTrials.gov #NCT04707872), an investigator-initiated, prospective trial, to examine the correlations between genome-wide molecular changes in endomyocardial biopsies (EMBs) and plasma dd-cfDNA. The present report analyzes the correlation of plasma dd-cfDNA with the gene expression in EMBs from 4 vanguard centers and compared these correlations with those in 604 kidney transplant biopsies in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703). Results. Top transcripts correlating with dd-cfDNA were related to genes increased in rejection such as IFNG-inducible genes (e.g., HLA-DMA), but also with genes induced by injury and expressed in macrophages (e.g., SERPINA1, HMOX1). In gene enrichment analysis, the top dd-cfDNA-correlated genes reflected inflammation and rejection pathways. Dd-cfDNA correlations with rejection genes in EMB were similar to those seen in kidney transplant biopsies, with somewhat stronger correlations for TCMR genes in hearts and ABMR genes in kidneys. However, the correlations with parenchymal injury-induced genes and macrophage genes were much stronger in hearts. Conclusions: In heart transplants in the Trifecta-Heart study, dd-cfDNA correlates significantly with molecular rejection but also with injury and macrophage infiltration, reflecting the proinflammatory properties of injured cardiomyocytes. The relationship supports the utility of dd-cfDNA in the clinical management of heart transplant recipients.

2024-07-19 | GSE272655 | GEO

Transcriptomic profiling of circulating T follicular helper cells in kidney transplant recipients

Project description:We compared the transcriptomic profile between patients without donor-specific HLA antibodies (DSA-), patients with donor-specific HLA antibodies without antibody-mediated rejection (DSA+ ABMR-) and patients with donor-specific HLA antibodies and antibody-mediated rejection (DSA+ ABMR+). We found that patient with DSA+ ABMR+ had a distinct transcriptomic profile compared to DSA- and DSA+ ABMR-, characterized by upregulation of genes encoding for germinal center T follicular helper cells function, T-B cell interaction and costimulatory molecules.

2021-07-01 | GSE134477 | GEO

Transcriptomic profiling of circulating T follicular helper cells (cTFH) and activated memory B cells (ABC) in kidney transplant recipients

2020-11-09 | GSE145503 | GEO

Subthreshold rejection activity in many kidney transplants currently classified as having no rejection.

Project description:Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower eGFR, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR respectively diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

2024-09-04 | GSE275126 | GEO

Defining a NK cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies

Project description:In lung transplantation, antibody-mediated rejection (AMR) diagnosed by ISHLT criteria is uncommon compared to other organs, and previous studies failed to find molecular AMR (ABMR) in lung biopsies. However, understanding of ABMR has changed with the recognition that ABMR in kidney transplants is often DSA-negative and associated with NK cell transcripts. After optimizing rejection-selective transcript sets (RSTS) in a training set (n = 488), the resulting algorithms separated an NK cell-enriched rejection-like state (NKRL) from TCMR/Mixed in a test set (n = 488). Applying this approach to all 896 TBBs distinguished three groups - No rejection; TCMR/Mixed; and NKRL. Like TCMR/Mixed, NKRL had increased expression of all-rejection transcripts, but NKRL had increased expression of NK cell transcripts, whereas TCMR/Mixed had increased effector T cell and activated macrophage transcripts. NKRL was usually DSA-negative and not recognized as AMR clinically. TCMR/Mixed was associated with CLAD, reduced FEV1, and short-term graft failure, but NKRL was not. Thus, some lung transplants manifest a molecular state similar to DSA-negative ABMR in kidney and heart transplants, but its clinical significance must be established.

2025-07-24 | GSE303535 | GEO

Genomics of Chronic Rejection

Project description:We hypothesized that T cell-mediated immune mechanisms play a role in two conditions; 1: donor-specific antibody (DSA) negative transplant glomerulopathy (TGP) and 2: interstitial fibrosis and tubular atrophy (IFTA) with inflammation (i>0). We investigated gene expression profiles of those biopsies compared to biopsies with antibody-mediated rejection(ABMR) and to biopsies with non-specific IFTA and no inflammation. DSA negative TGP and IFTA with inflammation biopsies have a unique molecular signature distinct to that seen in biopsies with ABMR and IFTA without inflammation with significant expression of cytotoxic and regulatory T cells.

2017-01-17 | GSE93658 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data