Impact of Animal Strain on Gene Expression in a Rat Model of Acute Cardiac Rejection
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE6342 | GEO | 2010/05/01
SECONDARY ACCESSION(S): PRJNA99645
REPOSITORIES: GEO
Similar Datasets
Project description:The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR). Additional analysis allowed for selection of 49 candidate genes uniquely associated with ACR, but only after accounting for the unexpectedly large effect of animal strain. Studies of ACR that examine gene expression in peripheral blood may be confounded by strain differences. These results indicate the need for study designs that eliminate or control for the large effect of genetic background on the transcriptome of immune cells. Using a rat heart transplant model microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC). Total RNA was isolated, reverse transcribed, labeled, and hybridized to oligonucleotide microarrays. In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ï?³ 3). Only 13 genes were affected by both strain and rejection, which was < 1% (13/1368) of all probesets differentially expressed in ACR. However, for PBMCs, strain alone affected 265 probesets (FDR 10% and FC ï?³ 3) and the addition of ACR had little further effect. Pathway analysis of strain effect in PBMCs associated gene expression differences with immune response, cell motility and cell death, functional themes that overlap with those related to ACR.
2010-05-01 | E-GEOD-6342 | biostudies-arrayexpress
Project description:Acute cellular rejection (ACR) is the major cause of intestinal graft loss. Little is known about the genetic response occurring in small bowel transplantation (SBTx) during ACR. We report the case of a 44 year-old female with short gut syndrome following multiple surgeries for familial adenomatous polyposis that underwent living-related SBTx. We obtained for the first time a gene expression profile of the intestinal graft during ACR. Microarray analysis revealed increased transcript levels for genes that match identically to an IFN? signature reported for activated plasmacytoid dendritic cells and T-cell chemotaxis and cytolysis correlating with the diagnosis of ACR. Keywords: disease state analysis
2008-03-12 | GSE5838 | 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:The histological evaluation of liver via biopsy remains as the standard for the diagnosis of both acute cellular rejection (ACR) and recurrent hepatitis C (RHC) after liver transplantation. Nevertheless, it is often difficult to diagnose ACR in HCV-positive recipients because of common co-existing and overlapping morphological changes with RHC. The aim of the study was to identify potential target genes for ACR in recipients with RHC. We analyzed 22 liver biopsy samples obtained from 21 HCV-positive recipients. The clinicopathological diagnoses for the biopsies were ACR-predominant with superimposed RHC in 9 samples (ACR group) and RHC with no ACR (non-ACR group) in the remaining. We compared the transcriptional alterations between the two groups with oligonucleotide microarray and selected 2206 genes which were significantly modulated in ACR. Subsequently we analyzed the regulatory networks in ACR using Ingenuity Pathway Analysis, and focused on 5 genes (IFNAR1, IL-12RB2, NFATC3, BMP2, and CASP8) from the core network as the target genes for ACR. In conclusion, our results demonstrated that novel transcriptome patterns of ACR and concurrent RHC were present and distinct from recipients with only RHC, suggesting that gene expression profiling may have a role in the diagnosis of ACR in recipients with hepatitis C. Keywords: Gene identification in ACR with recurrent HCV infection
2009-08-05 | GSE13440 | GEO
Project description:The histological evaluation of liver via biopsy remains as the standard for the diagnosis of both acute cellular rejection (ACR) and recurrent hepatitis C (RHC) after liver transplantation. Nevertheless, it is often difficult to diagnose ACR in HCV-positive recipients because of common co-existing and overlapping morphological changes with RHC. The aim of the study was to identify potential target genes for ACR in recipients with RHC. We analyzed 22 liver biopsy samples obtained from 21 HCV-positive recipients. The clinicopathological diagnoses for the biopsies were ACR-predominant with superimposed RHC in 9 samples (ACR group) and RHC with no ACR (non-ACR group) in the remaining. We compared the transcriptional alterations between the two groups with oligonucleotide microarray and selected 2206 genes which were significantly modulated in ACR. Subsequently we analyzed the regulatory networks in ACR using Ingenuity Pathway Analysis, and focused on 5 genes (IFNAR1, IL-12RB2, NFATC3, BMP2, and CASP8) from the core network as the target genes for ACR. In conclusion, our results demonstrated that novel transcriptome patterns of ACR and concurrent RHC were present and distinct from recipients with only RHC, suggesting that gene expression profiling may have a role in the diagnosis of ACR in recipients with hepatitis C. Keywords: Gene identification in ACR with recurrent HCV infection Of 22 liver biopsy samples, 9 represented the clinicopathological diagnoses for ACR-predominant with superimposed RHC (ACR group) and 13 represented the clinicopathological diagnoses for RHC with no ACR (non-ACR group) .
2010-05-15 | E-GEOD-13440 | biostudies-arrayexpress
Project description:Histological features of acute rejection can be detected in surveillance biopsies despite stable graft function and can negatively impact graft outcomes. However, routine surveillance biopsies for detection of subclinical rejection are not generally performed due to potential risks and costs associated with repeated biopsies. Noninvasive biomarkers are required to facilitate early detection of acute rejection and borderline changes. We examined the impact of histological abnormalities at 3-month in surveillance biopsies on graft outcomes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study. We then performed RNA sequencing on whole blood collected at the time of biopsy in 88 patients (22 vs. 66) to identify transcripts associated with histological abnormalities. Subjects with subclinical ACR or borderline ACR at 3 month (ACR-3) had higher risk of subsequent clinical acute rejection at 12 and 24 month (P < 0.05), more rapid functional decline (P < 0.05) and a decreased graft survival in adjusted cox analysis (P < 0.01) than patients with no abnormalities on 3-month biopsy. We then identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3. The gene set was then validated for diagnosis of ACR-3 using microarray data (N=65; 12 vs. 53; 26 overlapping with the RNAseq cohort).
2019-09-11 | GSE120397 | GEO
Project description:Histological features of acute rejection can be detected in surveillance biopsies despite stable graft function and can negatively impact graft outcomes. However, routine surveillance biopsies for detection of subclinical rejection are not generally performed due to potential risks and costs associated with repeated biopsies. Noninvasive biomarkers are required to facilitate early detection of acute rejection and borderline changes. We examined the impact of histological abnormalities at 3-month in surveillance biopsies on graft outcomes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study. We then performed RNA sequencing on whole blood collected at the time of biopsy in 88 patients (22 vs. 66) to identify transcripts associated with histological abnormalities. Subjects with subclinical ACR or borderline ACR at 3 month (ACR-3) had higher risk of subsequent clinical acute rejection at 12 and 24 month (P < 0.05), more rapid functional decline (P < 0.05) and a decreased graft survival in adjusted cox analysis (P < 0.01) than patients with no abnormalities on 3-month biopsy. We then identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3.
2019-09-11 | GSE120396 | GEO
Project description:Aims. Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. Methods. A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or â¥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n= 13); rejection â¥3A (RISHLT, n=13); 0 one month before ACR (BRISHLT, n=10). Results. We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples. Conclusion. Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipientsâ care.
2017-03-07 | E-MTAB-5136 | biostudies-arrayexpress
Project description:Acute cellular rejection (ACR) is the major cause of intestinal graft loss. Little is known about the genetic response occurring in small bowel transplantation (SBTx) during ACR. We report the case of a 44 year-old female with short gut syndrome following multiple surgeries for familial adenomatous polyposis that underwent living-related SBTx. We obtained for the first time a gene expression profile of the intestinal graft during ACR. Microarray analysis revealed increased transcript levels for genes that match identically to an IFN? signature reported for activated plasmacytoid dendritic cells and T-cell chemotaxis and cytolysis correlating with the diagnosis of ACR. Experiment Overall Design: sam1, sam2, sam3 (without signs of rejection) Experiment Overall Design: sam4, sam5, sam6 (with signs and symptoms of rejection , histology showed increasing lymphocyte infiltration in the lamina propria and epithelium)
2008-04-03 | E-GEOD-5838 | biostudies-arrayexpress
Project description:Recurrent hepatitis C virus (rHCV) is universal post-liver transplantation (LT), with accelerated fibrosis rates compared to non-transplanted patients. rHCV is associated with increased mortality and morbidity post-transplant and is a leading indication for re-transplantation. We hypothesized that miRNA expression profiles from liver grafts can distinguish severity of HCV recurrence and differentiate this from acute cellular rejection (ACR). Methods Using microarrays, we characterized global microRNA (miRNA) expression from patients with slow HCV fibrosis progression (F<2 Ishak), fast HCV fibrosis progression (F≥2 Ishak), ACR and non-HCV transplanted patients. Selected miRNA were analysed by quantitative PCR (qPCR) using both liver tissue and serum samples. Results We demonstrated changes in miRNA expression in patients with slow HCV fibrosis progression that were anti-fibrogenic, anti-angiogenic and anti-inflammatory in comparison to patients with fast HCV fibrosis progression. miRNA-146a, miRNA-19a, miRNA- 20a and miRNA-let-7e expression were increased in the slow HCV fibrosis progression group. In addition, comparison of patients with fast HCV progression against patients with ACR identified pro-fibrogenic pathways. qPCR analysis on liver tissue and serum confirmed the up-regulation of miRNAs in the slow HCV fibrosis progression group. Conclusion We demonstrate specific miRNA expression signatures that distinguish rate of progression of HCV recurrence and ACR post –liver transplantation. Pathway analysis indicates that specific miRNA may play a regulatory role in these processes. The miRNAs identified may act as potential biomarkers for HCV recurrence post-LT and help distinguish between ACR and recurrent HCV.
2013-09-17 | GSE40113 | GEO