Ontology highlight
ABSTRACT:
PROVIDER: PRJNA487207 | ENA |
REPOSITORIES: ENA
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Project description:Lung allograft rejection results in the accumulation of low molecular weight hyaluronic acid (LMW-HA), which further propagates inflammation and tissue injury. We have previously shown that therapeutic lymphangiogenesis in a murine model of lung allograft rejection reduced tissue LMW-HA and was associated with improved transplant outcomes. Herein we investigated the use of 4-Methylumbelliferone (4-MU), a known inhibitor of HA synthesis, to alleviate acute allograft rejection in a murine model of lung transplantation. We found that treating mice with 4-MU from day 20-30 post-transplant was sufficient to significantly improve outcomes, characterized by a reduction in T-cell mediated lung inflammation, LMW-HA content and improved pathology scores. In vitro, 4-MU directly attenuated activation, proliferation, and differentiation of naïve CD4+ T-cells into Th1 cells. As 4-MU has already been demonstrated to be safe for human use, we believe examining 4-MU for the treatment of acute lung allograft rejection may be of clinical significance.
2021-12-15 | GSE183142 | GEO
Project description:The Australian Chronic Allograft Dysfunction (AUSCAD) study is an ongoing single centre cohort study at Westmead hospital in Australia. In this section of the study, we aimed to identify biomarkers for allograft rejection in kidney transplant recipients, 3-months after their transplant. Our study recruited 123 patients, each having protocol renal allograft biopsies taken 3-months post transplantation.
2024-04-05 | GSE261892 | GEO
Project description:Transplant rejection is a major factor limiting allograft survival. CircRNAs are reported to be strongly associated with various diseases pathogenesis. However, the potential role of circRNAs in cardiac transplant rejection are rarely reported. Here, differentially expressed mRNAs and circRNAs were determined by microarrays in allogeneic cardiac allografts. Functional analysis was then performed and a full-scale functional blueprint of the circRNA-associated-ceRNA networks was constructed. Among the circRNA networks, circ23123 expression was negatively linked with cytolytic molecules of CD8+ T cells by targeting miR155-SOCS1 axis. We illustrated a new comprehensive view of circRNAs and their potential functional impact in cardiac transplantation. It may provide a prospective for therapeutic strategy on organ transplant rejection in the future.
2020-12-16 | GSE163261 | GEO
Project description:Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single cell RNA and T cell receptor sequencing on recipient derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with acute cellular rejection and compare them with T cells obtained from the same three patients after clinical treatment of rejection with high-dose, systemic glucocorticoids. At the time of acute cellular rejection, we find an oligoclonal expansion of cytotoxic CD8+ T cells, that all persist as tissue resident memory T cells following successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators following therapy with glucocorticoids. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in-situ expansion. These findings pose a potential biological mechanism linking acute cellular rejection to chronic allograft damage.
2021-10-15 | GSE185659 | GEO
Project description:BACKGROUND: Assessment of gene expression in peripheral blood may provide a noninvasive screening test for allograft rejection. We hypothesized that changes in peripheral blood expression profiles would correlate with biopsy-proven rejection and would resolve after treatment of rejection episodes. METHODS AND RESULTS: We performed a case-control study nested within a cohort of 189 cardiac transplant patients who had blood samples obtained during endomyocardial biopsy (EMB). Using Affymetrix HU133A microarrays, we analyzed whole-blood expression profiles from 3 groups: (1) control samples with negative EMB (n=7); (2) samples obtained during rejection (at least International Society for Heart and Lung Transplantation grade 3A; n=7); and (3) samples obtained after rejection, after treatment and normalization of the EMB (n=7). We identified 91 transcripts differentially expressed in rejection compared with control (false discovery rate <0.10). In postrejection samples, 98% of transcripts returned toward control levels, displaying an intermediate expression profile for patients with treated rejection (P<0.0001). Cluster analysis of the 40 transcripts with >25% change in expression levels during rejection demonstrated good discrimination between control and rejection samples and verified the intermediate expression profile of postrejection samples. Quantitative real-time polymerase chain reaction confirmed significant differential expression for the predictive markers CFLAR and SOD2 (UniGene ID No. 355724 and No. 384944). CONCLUSIONS: These data demonstrate that peripheral blood expression profiles correlate with biopsy-proven allograft rejection. Intermediate expression profiles of treated rejection suggest persistent immune activation despite normalization of the EMB. If validated in larger studies, expression profiling may prove to be a more sensitive screening test for allograft rejection than EMB. Experiment Overall Design: Case- control study with three groups. Patients with rejection (r1-r7), follow-up samples after treatment of rejection (post1-7), and controls with no rejection (con1-7)
2008-06-14 | E-GEOD-5967 | biostudies-arrayexpress
Project description:Improved understanding of lung transplant disease states is essential because failure rates are high, often due to chronic lung allograft dysfunction. However, histologic assessment of lung transplant transbronchial biopsies (TBBs) is difficult and often uninterpretable even with 10 pieces. All 242 single-piece TBBs produced reliable transcript measurements. Paired TBB pieces available from 12 patients showed significant similarity but also showed some sampling variance. Alveolar content, as estimated by surfactant transcript expression, was a source of sampling variance. To offset sampling variation, for analysis we selected 152 single-piece TBBs with high surfactant transcripts. Unsupervised archetypal analysis identified four idealized phenotypes (archetypes) and scored biopsies for their similarity to each: normal, T cell-mediated rejection (TCMR; T cell transcripts), antibody-mediated rejection (ABMR)-like (endothelial transcripts), and injury (macrophage transcripts). Molecular TCMR correlated with histologic TCMR. The relationship of molecular scores to histologic ABMR could not be assessed because of the paucity of ABMR in this population. Molecular assessment of single-piece TBBs can be used to classify lung transplant biopsies and correlated with rejection histology. Two or three pieces for each TBB will probably be needed to offset sampling variance.
2019-08-16 | GSE125478 | GEO
Project description:Gene expression data was analyzed to map with urine proteomics data gene expression data from kidney biopsies from kidney transplant patients with and without acute rejection, chronic allograft nephropathy and BK virus nephritis was used to study gene expression changes during acute rejection, chronic allograft nephropathy and bk virus nephropathy. Samples labeled STA16, STA22, STA14, and STA18 were included in the CAN vs no-CAN analysis as no-CAN samples as they also qualified as non-CAN samples.
2017-08-22 | GSE75693 | GEO
Project description:Microarrays were used to analyze the gene expression in peripheral blood and kidney allograft biopsies from patients with a kidney transplantation to get more insight in the molecular mechanisms underlying the different clinical phenotypes of kidney transplant rejection.
2019-08-15 | GSE129166 | GEO
Project description:The microbiota modulates skin allograft rejection
| PRJEB13722 | ENA
Project description:Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. Groups differed in median time post-transplant e.g. R3injury 99 days vs. R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts e.g. intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (e.g. hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR, R3injury, and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical ABMR were present in the population, and strategies that previously revealed antibody-mediated rejection (ABMR) in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.
2020-05-06 | GSE145780 | GEO