Transcription profiling of human endomyocardial biopsies before, during and after cardiac allograft rejection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER:
PROVIDER: S-DIXA-D-1147 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Cardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. Endomyocardial tissue samples were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Keywords: time course
2006-03-02 | GSE4315 | GEO
Project description:Cardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. Endomyocardial tissue samples were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Experiment Overall Design: Three subjects (subject number 1,8 and 12) Experiment Overall Design: Three timepoints (Before, during and after an rejection episode)
2007-12-12 | E-GEOD-4315 | biostudies-arrayexpress
Project description:AimsAllograft rejection following heart transplantation (HTx) is a serious complication even in the era of modern immunosuppressive regimens and causes up to a third of early deaths after HTx. Allograft rejection is mediated by a cascade of immune mechanisms leading to acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR). The gold standard for monitoring allograft rejection is invasive endomyocardial biopsy that exposes patients to complications. Little is known about the potential of circulating miRNAs as biomarkers to detect cardiac allograft rejection. We here present a systematic analysis of circulating miRNAs as biomarkers and predictors for allograft rejection after HTx using next-generation small RNA sequencing.Methods and resultsWe used next-generation small RNA sequencing to investigate circulating miRNAs among HTx recipients (10 healthy controls, 10 heart failure patients, 13 ACR, and 10 AMR). MiRNA profiling was performed at different time points before, during, and after resolution of the rejection episode. We found three miRNAs with significantly increased serum levels in patients with biopsy-proven cardiac rejection when compared with patients without rejection: hsa-miR-139-5p, hsa-miR-151a-5p, and hsa-miR-186-5p. We identified miRNAs that may serve as potential predictors for the subsequent development of ACR: hsa-miR-29c-3p (ACR) and hsa-miR-486-5p (AMR). Overall, hsa-miR-486-5p was most strongly associated with acute rejection episodes.ConclusionsMonitoring cardiac allograft rejection using circulating miRNAs might represent an alternative strategy to invasive endomyocardial biopsy.
| S-EPMC8120386 | biostudies-literature
Project description:Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures,and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]). Additional 22 biopsies were tested by PCR to validate the results. CXCL9, CXCL10, CXCL11, and IDO1 were the top differentially expressed genes, upregulated in AR. Lactoferrin (LTF) and CXCL1 were higher in APN and NP. No statistically significant difference in transcript levels was seen between culture-positive and culture-negative APN biopsies. Comparing the overall mRNA signature using Ingenuity pathway analysis, interferon-gamma emerged as the dominant upstream regulator in AR and allograft APN, but not in NP (which clustered separately). Our study suggests that chemokine pathways in graft APN may differ from NP and in fact resemble AR, due to a component of alloreactivity, resulting in variable response to antibiotic treatment. Therefore, cautious addition of steroids might help in resistant cases of graft APN.
| S-EPMC5256948 | biostudies-literature
Project description:In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation. Experiment Overall Design: biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral
| S-ECPF-GEOD-5462 | biostudies-other
Project description:Low levels of plasma adiponectin, an adipocytokine that possesses anti-inflammatory and antiatherogenic properties, frequently observed among obese subjects correlate with higher prevalence of several cardiovascular diseases. This study investigated whether adiponectin modulates allograft rejection in major histocompatibility complex class II-mismatched cardiac transplants.We heterotopically transplanted Bm12 allografts into adiponectin-deficient (APN-/-, C57BL/6 background) or wild-type (APN+/+) mice. Some APN-/- mice received adiponectin reconstitution by adenovirus. Histologic analyses assessed allograft rejection, and real-time reverse-transcriptase polymerase chain reaction evaluated the genes for cytokines/chemokines associated with the immune and inflammatory responses. In addition, we tested the effect of adiponectin on proliferation and cytokine/chemokine production in mouse T lymphocytes stimulated in vitro with anti-CD3 antibodies.Allografts transplanted to APN-/- mice showed severe acute rejection relative to transplants in APN+/+ hosts accompanied by increased accumulation of CD4- and CD8-positive T lymphocytes and Mac3-positive macrophages. Adiponectin provision by adenovirus in APN-/- mice reversed these exacerbated responses to allografting. The rejected allografts in APN-/- mice contained significantly higher levels of tumor necrosis factor-alpha, interferon-gamma, and regulated on activation normal t expressed and presumably secreted. Moreover, adiponectin significantly suppressed proliferation and production of tumor necrosis factor-alpha, interferon-gamma, regulated on activation normal t expressed and presumably secreted, monocyte chemotactic protein-1, and interferon-gamma inducible protein-10 in mouse T lymphocytes stimulated in vitro with anti-CD3 antibodies.These observations provide new mechanistic insight into immunoregulation in allograft recipients relative to obesity, an increasingly prevalent risk factor. Adiponectin may offer a new therapeutic target for allograft rejection after cardiac transplantation.
| S-EPMC2784664 | biostudies-literature
Project description:BackgroundCardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. However, this is an invasive procedure, which is unpleasant for the patient and carries a certain risk. Therefore, a sensitive non-invasive biomarker of acute rejection would be desirable.MethodsEndomyocardial tissue samples and serum were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients (11 men and 3 women) and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Genes showing up-regulation during rejection followed by normalization after the rejection episode were evaluated further with real-time RT-PCR. Finally, ELISA was performed to investigate whether change in gene-regulation during graft rejection was reflected in altered concentrations of the encoded protein in serum.ResultsThree potential cardiac allograft rejection biomarker genes, chemokine (C-X-C motif) ligand 9 (CXCL9), chemokine (C-X-C motif) ligand 10 (CXCL10) and Natriuretic peptide precursor A (NPPA), from the DNA microarray analysis were selected for further evaluation. CXCL9 was significantly upregulated during rejection (p < 0.05) and CXCL10 displayed a similar pattern without reaching statistical significance. Serum levels of CXCL9 and CXCL10 were measured by ELISA in samples from 10 patients before, during and after cardiac rejection. There were no changes in CXCL9 and CXCL10 serum concentrations during cardiac rejection. Both chemokines displayed large individual variations in the selected samples, but the serum levels between the two chemokines correlated (p < 0.001).ConclusionWe conclude, that despite a distinct up-regulation of CXCL9 mRNA in human hearts during cardiac allograft rejection, this was not reflected in the serum levels of the encoded protein. Thus, in contrast to previous suggestions, serum CXCL9 does not appear to be a promising serum biomarker for cardiac allograft rejection.
| S-EPMC1569871 | biostudies-literature
Project description:AimsSerial 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.MethodsA 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 ?3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ?3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10).ResultsWe 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.ConclusionMyocardial 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 recipients' care.
| S-EPMC5127573 | biostudies-literature
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:The molecular refinement of the diagnosis of heart allograft rejection based on whole-transcriptome analyses faces several hurdles that greatly limit its widespread clinical application. The targeted Banff Human Organ Transplant gene panel (B-HOT, including 770 genes of interest) has been developed to facilitate reproducible and cost-effective gene expression analysis of solid organ allografts. We aimed to determine in silico the ability of this targeted panel to capture the antibody-mediated rejection (AMR) molecular profile using whole-transcriptome data from 137 heart allograft biopsies (71 biopsies reflecting the entire landscape of histologic AMR, 66 non-AMR control biopsies including cellular rejection and non-rejection cases). Differential gene expression, pathway and network analyses demonstrated that the B-HOT panel captured biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cell-related genes), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions, endothelial activation) and networks reflecting the pathophysiological mechanisms underlying the AMR process previously identified in whole-transcriptome analysis. Our findings support the potential clinical use of the B-HOT-gene panel as a reliable proxy to whole-transcriptome analysis for the gene expression profiling of cardiac allograft rejection.
| S-EPMC10515212 | biostudies-literature