Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA348762 | ENA |
REPOSITORIES: ENA
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Project description:Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection
| PRJNA348761 | ENA
Project description:Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection [mRNA]
| PRJNA348763 | ENA
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: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:Sixty-five selected post-transplant biopsy samples (30 acute cellular rejection (AREJ 15 Banff-1, 15 Banff-2), 11 antibody mediated rejection (ABMR), 14 DGF, 10 PBx - protocol management biopsies - controls) were analyzed by using the Affymetrix GeneChip® miRNA Array.
2013-06-14 | GSE30282 | GEO
Project description:Background. The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression. Methods. Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative PCR.
2014-07-01 | GSE48971 | GEO
Project description:Background. The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression. Methods. Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative PCR.
2014-07-01 | GSE48969 | GEO
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:Sixty-five selected post-transplant biopsy samples (30 acute cellular rejection (AREJ 15 Banff-1, 15 Banff-2), 11 antibody mediated rejection (ABMR), 14 DGF, 10 PBx - protocol management biopsies - controls) were analyzed by using the Affymetrix GeneChip® miRNA Array. comparison between control group (protocol biopsies 3 month after TX) and indication biopsies (AREJ, ABMR and DGF)
2013-06-14 | E-GEOD-30282 | biostudies-arrayexpress
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