Single-cell transcriptomics of peripheral blood reveals a novel B-cell subset in renal allograft recipients with accommodation
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ABSTRACT:
PROVIDER: PRJNA732381 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14631721_1.fastq.gz | Fastqsanger.gz | |||
| SRR14631721_2.fastq.gz | Fastqsanger.gz |
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Project description:Kidney transplantation is a preeminent treatment for end-stage renal disease . The application of immunosuppressants is needed for kidney recipients to avoid allograft rejection but increase the risk of infection, and balance between rejection and infection is an important in clinical to reach the immune accommodation. Here, we use single-cell RNA sequencing to fully assess the immune status of peripheral mononuclear cells in kidney recipients. and compared the differences between kidney recipients and healthy people to describe the characteristics of the immune accommodation of kidney recipients. We found a novel B cell subset (CD19+IGKC+IGLC3lowTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of healthy people and verified by flow cytometry. which may have potential regulatory potential. Furthermore, we found that IL32 may increase the expression of CD19+IGKC+IGLC3lowTCL1A-CD127+ Bcells. In summary, we found that the CD19+IGKC+IGLC3lowTCL1A-CD127+B subgroup with immunomodulatory potential is inhibited in kidney recipients with accommodation state, and IL-32 has therapeutic potential for this.
2021-05-25 | GSE175429 | GEO
Project description:This experiment compare the transcriptional profile of CD8+CD45RClow Tregs from naive untreated rats compared to CD40Ig-treated tolerant allograft recipients.
2015-11-30 | E-MTAB-3535 | biostudies-arrayexpress
Project description:Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor. Transcriptional profiles of 40 renal allograft biopsy samples were analyzed using Illumina HumanRef-8 v3.0 BeadChips (Illumina, San Diego, CA). Expression profiles were investigated in total RNA isolated from biopsy samples of 18 patients with steroid responsive acute rejection and 18 patients with steroid resistant acute rejection. Four biopsies, taken during acute decrease of graft function but with no histomorphologic indication of rejection, were included as controls.
2013-05-21 | E-GEOD-47097 | biostudies-arrayexpress
Project description:In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft.
2017-09-01 | GSE83486 | GEO
Project description:The study comprises various components: We aim to screen out different gene expression profile in acute rejection on the kidney. We aim to screen out different gene expression profile in acute tubular necrosis on the kidney. We aim to screen out different gene expression profile in borderline change on the kidney. We aim to screen out different gene expression profile in non-rejection on the kidney. We aim to screen out different gene expression profile in presumed rejection on the kidney. We aim to screen out different gene expression profile in renal recipients with stable function. Results from the various study components can help to diagnose renal allograft dysfunction with different causes by distinct gene expression profile. Keywords: acute rejection, acute tubular necrosis, borderline change, non-rejection, presumed rejection, renal recipients with stable function,
2009-11-25 | GSE19130 | GEO
Project description:Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor.
2013-05-21 | GSE47097 | GEO
Project description:Transcriptomic analyses reveal regional signatures in lung allograft recipients
| PRJNA885405 | ENA
Project description:Background and objective: Long term outcomes of allograft recipients are compromised by the development of chronic lung allograft dysfunction (CLAD) or bronchiolitis obliterans syndrome (BOS) which initiates in the lung periphery. We established baseline transcriptomic profiles of both the large and small airway epithelial cells (referred as LAEC and SAEC, respectively) to identify regional differences irrespective of initiating disease. Methods: We obtained matched primary LAEC and SAEC from lung allograft recipients (n=4, 42.5±4.2 years) and established primary cultures. Bulk RNA sequencing was performed to determine differentially expressed genes. Results: We observed differences in the transcriptional program between LAEC and SAEC Transcription factors (TF) were ranked within the top ten differentially regulated genes. The most abundant TF families included C2H2-ZF, homeobox and bHLH. Upstream regulator analyses identified homeobox genes being significantly in LAEC. Protein-protein interaction network analysis emphasised the role of TFs (ISL1, MSX1, HOXA1, GATA6, ZNF423) in airway modulation. Additionally, functional enrichment analysis revealed the activation of chemotaxis, metalloendipeptidase/metallopeptidase activity and pro-inflammatory signatures (IL17 signalling and RAGE), in LAEC, while SAEC were characterised by elevated expression of surfactant metabolism related genes. Moreover, alveolar and club cells-related genes were expressed in SAEC, suggesting a lower airway-specific signature. Conclusion: Our analysis shows robust transcriptional differences between LAEC and SAEC. We suggest a potential role for homeobox TF family as well as the activation of the immune system in the biology of LAEC. Conversely, we observed an alveoli-like transcriptional signature in SAEC, including gas-exchange signals and surfactant metabolism; pathways involved in lung homeostasis.
2022-10-01 | GSE214434 | GEO
Project description:Compromised renal function after renal allograft transplantation often results in anemia in the recipient. Molecular mechanisms leading to anemia during acute rejection are not fully understood; inadequate erythropoietin production and iron deficiency have been reported to be the main contributors. To increase our understanding of the molecular events underlying anemia in acute rejection, we analyzed the gene expression profiles of peripheral blood lymphocytes (PBL) from four pediatric renal allograft recipients with acute rejection and concurrent anemia, using DNA microarrays containing 9000 human cDNA clones (representing 7469 unique genes). In these anemic rejecting patients, an 'erythropoiesis cluster' of 11 down-regulated genes was identified, involved in hemoglobin transcription and synthesis, iron and folate binding and transport. Additionally, some alloimmune response genes were simultaneously down-regulated. An independent data set of 36 PBL samples, some with acute rejection and some with concurrence of acute rejection and anemia, were analyzed to support a possible association between acute rejection and anemia. In conclusion, analysis using DNA microarrays has identified a cluster of genes related to hemoglobin synthesis and/or erythropoeisis that was altered in kidneys with renal allograft rejection compared with normal kidneys. The possible relationship between alterations in the expression of this cluster, reduced renal function, the alloimmune process itself, and other influences on the renal transplant awaits further analysis.
2005-11-01 | E-SMDB-2730 | biostudies-arrayexpress
Project description:The study comprises various components: We aim to screen out different gene expression profile in acute rejection on the kidney. We aim to screen out different gene expression profile in acute tubular necrosis on the kidney. We aim to screen out different gene expression profile in borderline change on the kidney. We aim to screen out different gene expression profile in non-rejection on the kidney. We aim to screen out different gene expression profile in presumed rejection on the kidney. We aim to screen out different gene expression profile in renal recipients with stable function. Results from the various study components can help to diagnose renal allograft dysfunction with different causes by distinct gene expression profile. Keywords: acute rejection, acute tubular necrosis, borderline change, non-rejection, presumed rejection, renal recipients with stable function, Samples GSM456771-GSM456800: This study has been accomplished with 15 patients of acute rejection on the kidney.Technical replicates: 2 replicates(except AR10 and AR13) Samples GSM456801-GSM456810: This study has been accomplished with 5 patients of acute tubular necrosis on the kidney. Technical replicates: 2 replicates(except ATN4) Samples GSM456811-GSM456831: This study has been accomplished with 11 patients of borderline change on the kidney.Tecnical replicates:2 replicates(except BL8 and BL11) Samples GSM456833-GSM456850: This study has been accomplished with 9 patients of non-rejection on the kidney.Technical replicates: 2 replicates Samples GSM456851-GSM456864: This study has been accomplished with 7 patients of presumed rejection on the kidney.Technical replicates: 2 replicates Samples GSM456865-GSM456894: This study has been accomplished with 15 patients of renal recipients with stable function.Technical replicates: 2 replicates
2010-06-25 | E-GEOD-19130 | biostudies-arrayexpress