IDENTIFYING KEY DRIVER GENES OF INNATE IMMUNE PATHWAYS AS NOVEL THERAPEUTIC TARGETS IN RENAL ALLOGRAFT REJECTION
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138043 | GEO | 2020/11/03
REPOSITORIES: GEO
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Project description:Acute allograft rejection is a leading cause for the failure of organ allotransplantation. Identifying the genes involved in the rejection process provides clues to study the mechanisms, and to provide specific gene targets for monitoring, predicting and preventing acute allograft rejection. Using a mice model of skin acute allograft rejection and SAGE method, we analyzed gene expression in the CD4+ T cells of the mice, the cell type known to play critical roles in acute allograft rejection. Our study identifies 402 SAGE tags significantly different from these from the control. From these SAGE tags, we identified 91 increasingly and 85 decreasingly expressed genes, and many genes have not been linked with acute allograft rejection before. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance and signal transduction are among the most frequently changed functional groups. Our study provides a genome-wide view for the genes involving acute allograft rejection in the CD4+ T cells, and indicates that acute allograft rejection involves multiple genes in different functional categories. The genes identified from the study provide candidates for further studying the mechanisms and for monitoring, predicting and preventing acute allograft rejection.
2010-03-01 | GSE14540 | GEO
Project description:Acute allograft rejection is a leading cause for the failure of organ allotransplantation. Identifying the genes involved in the rejection process provides clues to study the mechanisms, and to provide specific gene targets for monitoring, predicting and preventing acute allograft rejection. Using a mice model of skin acute allograft rejection and SAGE method, we analyzed gene expression in the CD4+ T cells of the mice, the cell type known to play critical roles in acute allograft rejection. Our study identifies 402 SAGE tags significantly different from these from the control. From these SAGE tags, we identified 91 increasingly and 85 decreasingly expressed genes, and many genes have not been linked with acute allograft rejection before. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance and signal transduction are among the most frequently changed functional groups. Our study provides a genome-wide view for the genes involving acute allograft rejection in the CD4+ T cells, and indicates that acute allograft rejection involves multiple genes in different functional categories. The genes identified from the study provide candidates for further studying the mechanisms and for monitoring, predicting and preventing acute allograft rejection. Female mice of 6-10 week age were used for the study. BALB/c mice (H-2d) and BALB/c severe combined immunodeficient (SCID) mice were from the animal facility of Shandong University (Jinan, China). C57BL/6 (H-2b, B6) were from Vitalriveri Co. ltd (Beijing, China). Mice were maintained in a pathogen-free animal environment during the experimental process. The use of mice for the study was approved by the Institutional Animal Experimental Committee, and animal care and surgical procedures were performed in compliance with the standard animal experimental protocols of Shandong University School of Medicine. The process of generating skin acute allograft rejection followed the established procedure (12). Briefly, dorsal skin of C57BL/6 was transplanted onto the dorsal thorax of BALB/c SCID mice under sterile condition (allotransplant). As a control, dorsal skin of BALB/c mice was transplanted to BALB/c SCID mice (autotransplant). After 28 days of transplantation, CD4+ T cells were harvested from the spleens of BALB/c mice by using the mouse CD4+ T cells enrichment columns (R&D) with the purity >90% as measured by flow cytometry and 8x106 purified CD4+ T cells were adoptively injected into each transplanted mice via the lateral tail vein. The skin graft in each transplanted mice was then monitored daily. The skin graft was considered to fully reject when more than 50% of the skin became necrosis. SAGE Analysis Upon 14 days post CD4+ T cell transferring, CD4+ T cells were collected from the spleens of five mice in each group with adaptive CD4 T cell transferring using the same process described above. Total RNA was extracted from the purified cells by using Trizol reagent (Invitrogen) and mRNA was purified from the total RNA using oligo dT beads (Invitrogen). cDNA was synthesized by using MMLV reverse transcriptase and oligo(dT) primers (MBI-add full name). SAGE libraries from 4 allotransplant and autotransplant groups were constructed following the standard procedure (13). For each SAGE library, 1,200 sequences were collected through an ABI 3730 DNA sequencer (Applied BioSystems). SAGE tags were extracted from the sequences by using the SAGE2000 software (Invitrogen).
2010-02-28 | E-GEOD-14540 | biostudies-arrayexpress
Project description:Transplantation is currently the best treatment option for end-stage renal disease (ESRD) patients. However, acute rejection (AR) is the main source of failure in renal transplantation. The current gold standard for diagnosis of AR involves renal biopsy, but it is invasive, time consuming, costly and inconvenient. Sensitive and less invasive detection of AR episodes in renal transplant patients is essential to preserve the allograft function. Here, we applied isobaric tags for relative and absolute quantisation (iTRAQ) mass spectrometry to analyse serum protein expression in AR patients and healthy controls. Overall, 1399 proteins were identified. Using a cut-off of Q<0.05 and a fold change > 1.2 for the expressed variation, 109 proteins showed distinct differential expression between the AR and control groups, of whom 72 were upregulated and 37 were downregulated. Several proteins, such as properdin, keratin 1, lipoprotein (a) and vitamin D-binding protein, may play roles in the pathogenesis of AR. This study focused on iTRAQ-based proteomic profiling of serum samples in AR. Insights from our work might help advance our understanding of the molecular mechanisms of AR and identify potential novel biomarkers of AR for further characterization.
2021-09-08 | PXD015336 | Pride
Project description:Early development of acute rejection after kidney transplantation is associated with diminished long-term graft survival. Predicting early acute rejection (EAR) at the time of transplant is important to risk-stratify patients and titrate immunosuppression accordingly. We performed whole-blood RNA sequencing at the time of transplant in 235 kidney transplant recipients enrolled in a prospective-cohort study [one discovery set (N=81), two validation sets (N=74 and N=80)] and evaluated the relationship with EAR and graft loss. We identified a blood based 23-gene set in recipients at the time of transplant that predicts the risk of EAR and is associated with late AR and allograft loss. This gene set is an important new tool to risk-stratify recipients before kidney transplantation and help guide immunosuppressive therapy accordingly.
2019-10-01 | GSE112927 | GEO
Project description:Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining “molecular Banff” signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However, the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set here comprises a small validation batch of renal allograft biopsies for clinical indications plus control normal kidney samples from patients at Hôpital Tenon, Paris (second batch) that complements the first batch of 60 samples. We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Keywords: disease state analysis 4 renal allograft core biopsies for clinical indications with different histopathological diagnoses according to Banff'97 criteria and 2 normal kidney samples.
2009-02-24 | E-GEOD-9492 | biostudies-arrayexpress
Project description:Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining âmolecular Banffâ signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However, the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set comprises all renal allograft biopsies for clinical indications from patients at Hôpital Tenon, Paris (February 2003 until September 2004) and few respective patients from Hôpital Bicêtre, Paris, Hôpital Pellegrin, Bordeaux, and Hôpital Dupuytren, Limoges, plus control normal kidney samples from Hôpital Tenon, Paris, France (first batch). We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Experiment Overall Design: 47 renal allograft core biopsies for clinical indications with different histopathological diagnoses according to BANFF'97 criteria, and 13 normal kidney samples as controls.
2009-02-28 | E-GEOD-9489 | biostudies-arrayexpress
Project description:Self-reactive antibodies cloned from B cells infiltrating in a human renal allograft were subjected to IP-mass spectrometry using nuclear lysates of HEp-2 cells.
2021-04-27 | PXD022989 | Pride
Project description:Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining M-bM-^@M-^\molecular BanffM-bM-^@M-^] signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However, the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set comprises all renal allograft biopsies for clinical indications from patients at HM-CM-4pital Tenon, Paris (February 2003 until September 2004) and few respective patients from HM-CM-4pital BicM-CM-*tre, Paris, HM-CM-4pital Pellegrin, Bordeaux, and HM-CM-4pital Dupuytren, Limoges, plus control normal kidney samples from HM-CM-4pital Tenon, Paris, France (first batch). We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Keywords: disease state analysis Keywords: Expression profiling by array 16 renal allograft core biopsies for clinical indications with different histopathological diagnoses according to BANFF'97 criteria (additional samples associated with GSE9489)
2009-08-27 | E-GEOD-17861 | biostudies-arrayexpress
Project description:Rat corneal allograft rejection models were established to investigate the effects and mechanisms of resveratrol on corneal allograft rejection after corneal transplantation.
2023-07-10 | GSE236626 | GEO
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