Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA270826 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Acute rejection in cardiac transplant patients is still a contributing factor to limited survival of the implanted heart. Currently there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplantation acute rejection, which would be of great importance for personalizing immunosuppressive treatment. Within the Biomarkers in Transplantation initiative, the predictive biomarker discovery focused on data and samples collected before or during transplantation such as: clinical variables, genes and proteins from the recipient, and genes from the donor. Based on this study, the best predictive biomarker panel contains genes from the recipient whole blood and from donor endomyocardial tissue and has an estimated area under the curve of 0.90. This biomarker panel provides clinically relevant prediction power and may help personalize immunosuppressive treatment and frequency of rejection monitoring.
2017-09-29 | GSE33970 | GEO
Project description:Liver transplantation is the only lifesaving therapy for patients with irreversible liver failure, and 30% of the recipients experience acute rejection in the first 12 months following transplantation. Acute rejection is diagnosed by core needle biopsy and noninvasive methods for predicting acute rejection could improve clinical care. MicroRNAs (miRNAs) are emerging as biomarkers of clinically significant events. We investigated whether circulating extracellular miRNA profiles in sera matched to liver allograft biopsies predict human liver allograft status. Small RNA sequencing and TaqMan low-density array analysis of RNA from biopsy matched sera identified that liver specific miR-122, and miRs -885, -210, -194, 193b, -192, -148a, -34a and -22 distinguish patients with acute rejection biopsies from those with biopsies without rejection features (false discovery rate of <0.15). We measured absolute levels of these informative 9 miRNAs using quantitative real-time PCR assays. Receiver-operating-characteristic (ROC) curve analysis of circulating levels of miRNA levels validated that all 9 miRNAs discriminate patients with acute rejection in their biopsies from those without rejection in their biopsies (P <0.01 to P<0.0001). A parsimonious diagnostic signature of miR-122 and miR-194 was diagnostic of acute rejection with a sensitivity of 79% (95% confidence interval [CI], 49% to 95%) and a specificity of 88% (95% CI, 64% to 99%) (area under the curve, 0.91; 95% CI, 0.81 to 1.00; P<0.001 by ROC curve analysis). Our findings suggest that a molecular signature of miR-122 and miR-194 in serum offers a noninvasive means of diagnosing acute rejection including mild forms in human liver allografts.
2019-06-30 | GSE69579 | GEO
Project description:Graft acceptance without the need for immunosuppressive drugs is the ultimate goal of transplantation therapy. In murine liver transplantation, allografts are accepted across major histocompatibility antigen complex barriers without the use of immunosuppressive drugs and constitute a suitable model for research on immunological rejection and tolerance. MicroRNA (miRNA) has been known to be involved in the immunological responses. In order to identify mRNAs in spontaneous liver allograft tolerance, miRNA expression in hepatic allografts was examined using this transplantation model. According to the graft pathological score and function, miR-146a, 15b, 223, 23a, 27a, 34a and 451 were upregulated compared with the expression observed in the syngeneic grafts. In contrast, miR-101a, 101b and 148a were downregulated. Our results demonstrated the alteration of miRNAs in the allografts and may indicate the role of miRNAs in the induction of tolerance after transplantation. Furthermore, our data suggest that monitoring the graft expression of novel miRNAs may allow clinicians to differentiate between rejection and tolerance. A better understanding of the tolerance inducing mechanism observed in murine hepatic allografts may provide a therapeutic strategy for attenuating allograft rejection.
2014-10-21 | GSE52164 | GEO
Project description:Graft acceptance without the need for immunosuppressive drugs is the ultimate goal of transplantation therapy. In murine liver transplantation, allografts are accepted across major histocompatibility antigen complex barriers without the use of immunosuppressive drugs and constitute a suitable model for research on immunological rejection and tolerance. MicroRNA (miRNA) has been known to be involved in the immunological responses. In order to identify mRNAs in spontaneous liver allograft tolerance, miRNA expression in hepatic allografts was examined using this transplantation model. According to the graft pathological score and function, miR-146a, 15b, 223, 23a, 27a, 34a and 451 were upregulated compared with the expression observed in the syngeneic grafts. In contrast, miR-101a, 101b and 148a were downregulated. Our results demonstrated the alteration of miRNAs in the allografts and may indicate the role of miRNAs in the induction of tolerance after transplantation. Furthermore, our data suggest that monitoring the graft expression of novel miRNAs may allow clinicians to differentiate between rejection and tolerance. A better understanding of the tolerance inducing mechanism observed in murine hepatic allografts may provide a therapeutic strategy for attenuating allograft rejection. B10.BR mice were used as donors and B10.D2 mice were used as recipients. Liver allo-transplantation surgery on the mice was performed in this combination. Three mice from each group were sacrificed, and the liver grafts were removed on days 5, 8, 14 and 100 after transplantation. Total RNA, including miRNA was isolated. 100ng of total RNA was labeled by Cy3 and used as probe for hybridization to the microarray.
2014-10-21 | E-GEOD-52164 | biostudies-arrayexpress
Project description:To investigate whether differentially expressed microRNAs in peripheral blood could be associated with clinically significant, histologically proven acute cellular rejection after liver transplantation, a microRNA microarray screening was performed with RNA isolated from PaxGene whole blood samples from patients with ACR within the first three postoperative weeks and from patients without clinical signs of rejection within the first 6 months after transplantation.
2016-12-24 | GSE65492 | GEO
Project description:Increased levels of donor-derived cell-free DNA (dd-cfDNA) in recipient plasma have been associated with acute cellular rejection (ACR) after heart transplantation. DNA sequence differences have been used to distinguish between donor and recipient cfDNA but epigenetic differences could also potentially identify dd-cfDNA. This study aimed to assess the feasibility of using ventricle-specific methylation patterns in human cfDNA as an alternative biomarker for ACR in cardiac transplantation.
2020-06-18 | GSE152648 | GEO
Project description:Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
2016-09-24 | GSE87301 | GEO
Project description:In transplantation, there is a critical need for non-invasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor specific exosomes into recipient circulation/ bodily fluids, and that the quantitation and profiling of their intra-exosomal cargoes would constitute a novel biomarker platform for monitoring rejection. We tested this hypothesis in a human into mouse xenogeneic islet transplant model, and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, islet transplant exosomes in recipient blood were quantified over long-term follow-up using anti-human leukocyte antigen (HLA) antibody that is only expressed on human islets (p=1.6x10-14). Transplant islet exosomes were purified using anti-HLA antibody conjugated beads and their cargoes contained bona fide islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to significant decrease in transplant islet exosome signal (p=4x10-15), along with distinct changes in its microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet (n=5) and renal (n=5) transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up (up to 5 years; p=0.0001). Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a non-invasive window into the conditional state of the transplant tissue.
2016-10-18 | GSE88845 | GEO
Project description:In transplantation, there is a critical need for non-invasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor specific exosomes into recipient circulation/ bodily fluids, and that the quantitation and profiling of their intra-exosomal cargoes would constitute a novel biomarker platform for monitoring rejection. We tested this hypothesis in a human into mouse xenogeneic islet transplant model, and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, islet transplant exosomes in recipient blood were quantified over long-term follow-up using anti-human leukocyte antigen (HLA) antibody that is only expressed on human islets (p=1.6x10-14). Transplant islet exosomes were purified using anti-HLA antibody conjugated beads and their cargoes contained bona fide islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to significant decrease in transplant islet exosome signal (p=4x10-15), along with distinct changes in its microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet (n=5) and renal (n=5) transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up (up to 5 years; p=0.0001). Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a non-invasive window into the conditional state of the transplant tissue.
2016-10-18 | GSE88844 | 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