HCMV_Resistance-mutations_Evolution
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ABSTRACT:
PROVIDER: PRJEB36759 | ENA |
REPOSITORIES: ENA
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Project description:Monitoring human cytomegalovirus populations in hematopoietic stem cell (HSCs) transplant patients
| PRJEB39015 | ENA
Project description:Profiling the blood compartment of Hematopoietic Stem Cell Transplant patients during Human Cytomegalovirus reactivation
| PRJNA679293 | 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 | GSE88845 | GEO
Project description:Genotyping human cytomegalovirus populations in a paediatric HSCT
| PRJEB38333 | ENA
Project description:In this study we employed transcriptome mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response. The flow cytometry data confirms depletion of specific cell subsets in response to ATG induction and immunosuppression with sustained decreases in CD4 as well as CD8 cell subsets. A series of T cell activation markers were expressed from Pre-Tx to 12 weeks indicating the evolution of immunity including expansion of CD45RO+CD62L- effector memory cells. Serial whole blood transcript monitoring demonstrated over 2000 differentially expressed genes, with over 80 percent down-regulated Post-Tx. However, cell subset analysis revealed a unique spectrum of subset-specific gene expression with time-dependent changes, with contrasting significant Post-Tx gene upregulation. Our results provide a unique view of the complex evolution of immune/inflammatory molecular networks marking the early post transplant immune response. A critical finding is that analysis of the constituent blood cell subsets provides an entirely new level of detail revealing the nature of this process, effectively deconvoluting the changes that are otherwise lost in the noise of cellular complexity of whole blood. Keywords: kidney transplantation, peripheral blood, DNA microarrays, acute kidney rejection, cell subsets, flow cytometry, serial monitoring We employed Affymetrix HG-U133 Plus 2.0 GeneChips for mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response.
2010-11-01 | E-GEOD-24223 | biostudies-arrayexpress
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:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pre-transplant genetic susceptibility is evident in adult TA-TMA patients at the level of TMA-associated variants and further investigated the association of genetic variants with clinical outcomes. We studied 30 patients with TA-TMA at a median of 73 (9-540) post-transplant days, donors of 18/30 patients and 30 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pre-transplant peripheral blood was analyzed by targeted next generation sequencing for complement regulatory genes and ADAMTS13. Donors presented significantly lower frequency of rare variants (p=0.049) and variants in exonic/splicing/UTR regions (p=0.025), compared to TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13 (p=0.001), CD46 (p=0.002), CFH (p=0.010) and CFI (p=0.031). Pathogenic variants were found in ADAMTS13, CFH, CFI and CFB, while homozygous pathogenic variants in ADAMTS13 and CFB were evident in only 4 TA-TMA patients (p=0.038). Patients refractory to conventional treatment (70%) were significantly (p=0.045) enriched for variants in exonic/splicing/UTR regions compared to responders. Nineteen of 30 patients (63%) succumbed to transplant-related mortality, which was also associated with significantly (p=0.012) increased frequency of variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pre-transplant genomic screening may be useful to intensify monitoring and early intervention in high-risk patients.
2019-04-18 | E-MTAB-7848 | biostudies-arrayexpress
Project description:Mining the Human Urine Proteome for Monitoring Renal Transplant Injury
| PRJNA305092 | ENA
Project description:Malignancies represent the third leading cause of post-transplant mortality worldwide. The main challenge for transplant physicians is a timely diagnosis of this condition. The aim of the study was to identify a soluble diagnostic marker for monitoring the development of post-transplant malignancies. This is a multicentre, observational, perspective, case-control study. We enrolled 47 patients with post-transplant solid neoplasia. As a control group we employed 106 transplant recipients without a history of neoplasia and matched them with cases for the main demographic and clinical features. We investigated the transcriptomic profiles of peripheral blood mononuclear cells from kidney graft recipients with and without post-transplant malignancies enrolled in two of the participating centres, randomly selected from the whole study population. Microarray results were confirmed by quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in the remaining patients from the same transplant centres and validated in a further independent group enrolled in two different transplant centres. We identified 535 differentially expressed genes comparing patients with and without post-transplant malignancies (fold change ≥2.5; false discovery rate <5%). The cancer pathway was closely related to gene expression data, and one of the most down-regulated genes in this pathway was interleukin-27 (IL-27), a cytokine regulating anti-tumour immunity. Quantitative PCR and ELISA confirmed the microarray data. Interestingly, IL-27 plasma levels were able to discriminate patients with post-transplant neoplasia with a specificity of 80% and a sensitivity of 81%. This observation was confirmed in an independent set of patients from two different transplant centres. Our data suggest that IL-27 may represent a potential immunological marker for the timely identification of post-transplant neoplasia.
2018-11-28 | GSE94424 | GEO
Project description:MRD screening in Human B-ALL: monitoring B-cell repertoires in longitudinal samples of patients.
2015-09-04 | E-ERAD-391 | biostudies-arrayexpress