Expression data from biopsies of CIT study patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Pilib Ó Broin
PROVIDER: E-GEOD-72355 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We aimed to investigate the effect of increased cold ischemia time (CIT) on gene expression profiles of implantation and clinically indicated biopsies early after transplantation and the impact of basiliximab (BAS) versus rabbit antithymocyte globulin (rATG) induction therapies on clinical outcomes and intragraft molecular features
2015-09-10 | GSE72355 | GEO
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens. Total of 28 arrays included in this study, which corresponding to 9 individuals with paired pre/post treatment samples and an additional 10 untreated control individuals. pair_analysis_normData.txt for paired analysis of pre/post treatment; ordinary_analysis_normData.txt for non-paired analysis include all samples, except for 38 Pax V0 and 56 Pax V1, which shows technicial bias and lowest array quality, hence removed from analysis.
2011-08-29 | E-GEOD-31729 | biostudies-arrayexpress
Project description:The objective of this study was to identify specific gene expression profiles able to predict the response of rheumatoid arthritis patients treated with methotrexate /abatacept (Aba). Thirty six RA patients were received Abatacept. The drug efficacy was evaluated with the DAS28 score after 6 months of treatment according to the EULAR response criteria. Among 36 Aba RA patients, 17 were responders and 19 were classified as no-responders. A blood sample was carried out in patients just before the first injection of treatment in PaxGene tubes. Two color experiments : patient(Cy5)/Control pool (Cy3).
2017-05-17 | E-GEOD-68215 | biostudies-arrayexpress
Project description:Glomerular abnormalities have been demonstrated in kidney biopsies of patient after orthotopic liver transplantation (OLT). We hypothesize that these changes exist prior to OLT and may play a role in the development of renal failure after OLT. We use gene expression microarrays to investigate the mechanism of kidney disease in patients listed for OLT. Gene expression profiles of biopsies of cirrhotic patients were compared with pre-implantation living donor biopsies. Glomerular abnormalities were seen in 92% of the biopsies, the most common being increase in mesangial matrix. Electron microscope showed effacement of podocytes (93%) and duplication (35%) and widening of glomerular basement membrane (45%). Gene Ontology analysis revealed significant up-regulation of genes implicated in immune response, including T-cell, leucocyte and platelet activation and differentiation. Pathogenesis-based transcripts analysis revealed significantly increased expression of cytotoxic T-cell, macrophage, B-cell, natural killer cell, and endothelial cell associated transcripts, indicating an ongoing inflammatory immune response. Eight patients with cirrhotic livers listed for transplantation were referred to the kidney transplant clinic at Montefiore Medical Center, Bronx, New York, for evaluation of renal dysfunction between April 2010 and March 2013. Patients consented prior to clinically indicated kidney biopsy for enrollment into the study. Information and lab results were collated for each patient including: age, sex, race, etiology of liver disease, history of diabetes mellitus (DM) and hypertension (HTN), metabolic profile, liver function tests, glycosylated hemoglobin (HgbA1c), C3 and C4 complement concentrations, antinuclear antibody titers and spot urine protein to creatinine ratio. Patients completed a 24-hr urine collection for protein and creatinine, which was used to assess proteinuria and creatinine clearance. eGFR was calculated using the Modified Diet of Renal Disease (MDRD) formula. Hematuria was defined as presence of any red cells in urine analysis. Proteinuria was defined as protein excretion of greater than 100mg in 24 hour. HTN and DM were defined by use of anti-hypertensive and insulin or oral hypoglycemic agents respectively in past or at time of kidney biopsy. Biopsies from cirrhotic patients were then compared to nine pre-implantation biopsies from living kidney donors. The de-identified patient clinical characteristics are provided in each sample records; For Hematuria, HTN, MM (mesangial matrix expansion), MC (mesangial cell increase), II (interstitial inflammation), podocyte, BM (basement membrane thickening), the value 0 and 1 represents 'ABSENT' and 'PRESENT', respectively. For C3 and C4, the value 0 and 1 represents NORMAL and LOW C3 (or C4) LEVELS, repectively. For TA (tubular atrophy), IF (interstital fibrosis), AS (arteiosclerosis), the value 0, 1, and 2 represents ABSENT, PRESENT MILD, and PRESENT MODERATE, respectively. For IgG, IgA, IgM, C, and EmPE, the values represent 1 (ABSENT), 1 (MILD STAINING), 2 (MODERATE), 3 (SEVERE), NA (NOT AVAILABLE), P (PENDING). For BMWId, BMd, and EDD, the values represent 0 (ABSENT), 1 (PRESENT), NA (NOT AVAILABLE), P (PENDING).
2013-09-17 | E-GEOD-50892 | biostudies-arrayexpress
Project description:We study the global gene expression profiles of TGP patients with or without graft loss to determine if a clinical and/or gene expression profile can predict allograft survival. Transplant glomerulopathy (TGP) carries a poor prognosis and is associated with decreased allograft survival. In a large series of kidney transplant recipients, graft loss was observed in 38% of TGP patients at 5 years compared to 5% in patients without TGP. Among patients with TGP, predictors of poor outcome included C4d deposition in the peritubular capillaries, higher serum creatinine and proteinuria at diagnosis, the severity of interstitial fibrosis, and GBM duplication (higher Banff M-bM-^@M-^Xchronic glomerulopathy [cg]M-bM-^@M-^Y score), and the presence of DSA. However, the importance of microvascular inflammation determined by peritubular capillaritis (ptc) and glomerulitis (g) scores and the strength of DSA has not been explored thoroughly. We have recently reported the intragraft gene expression profiles of TGP patients, with or without DSA. However, the association between gene expression profiles of biopsies and the allograft survival has not been investigated. In this study, in addition to known clinical and demographic factors associated with poor outcomes in TGP, we specifically aimed to investigate if intragraft gene expression profiles by microarrays, microvascular inflammation scores, and the strength of DSA determined by mean fluorescence intensity (MFI) values could predict allograft loss in TGP patients. The study population was derived from renal allograft biopsies diagnosed with TGP at Montefiore Medical Center, Bronx, NY from January 2009 to December 2012. All biopsies were clinically indicated for elevated creatinine or proteinuria. A retrospective chart review was conducted to record clinical, demographic, immunological, and histopathological parameters and graft outcomes. Graft loss was defined as requiring dialysis and/or retransplantation during follow-up. Of the 525 patients who underwent clinically indicated transplant kidney biopsies, 52 patients (10%) had diagnosis of TGP. Median follow up time after the biopsy was 23 months (range, 1-46). Seventeen patients (32%) lost their allografts (defined by return to dialysis or re-transplantation) at a median time of 16 months (range, 1-44). A subgroup of patients who were enrolled in the IRB-approved M-bM-^@M-^\Immune Monitoring StudyM-bM-^@M-^] and had clinically indicated biopsy samples were included in the analysis. A total of 28 biopsy samples (8 graft loss and 20 functioning allograft) were used for gene expression profiling.
2014-06-18 | E-GEOD-58601 | biostudies-arrayexpress
Project description:The presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection. Clinical and histological features, and gene expression profiles of kidney biopsy and blood samples of donor-specific antibody (DSA)+ patients without rejection were compared to antibody-mediated rejection (AMR) patients to elucidate the mechanisms involved in prevention of AMR. Of the 71 DSA+ patients, 46 had diagnosis of AMR and 25 did not show rejection. 50 DSA- patients without rejection were used as control. A subgroup of patients with available biopsy (n=61) and blood samples (n=54) were analyzed by microarrays. Both, DSA+/AMR+ and DSA+/AMR- biopsies showed increased expression of gene transcripts associated with cytotoxic T, natural killer cells, macrophages, interferon-gamma and rejection compared to DSA- biopsies. Regulatory T cell transcripts were up-regulated in DSA+/AMR+ and B cell transcripts in DSA+/AMR- biopsies. Whole blood gene expression analysis showed increased immune activity in only DSA+/AMR+ patients. There were no differentially expressed tolerant genes studied (n=14) in the blood or biopsy specimens of DSA+/AMR- patients. During a median 36 months follow-up, 4 DSA+/AMR- patients developed AMR, 12 continued to have DSAs but 9 lost DSAs. Gene expression profiles did not predict the development of AMR or persistence of DSAs. These results indicate increased immune activity in DSA+/AMR- biopsies despite lack of histologic findings of rejection. All clinically indicated kidney transplant biopsies performed at our institution after January 2009 were reviewed and 263 patients with anti-HLA antibody testing at the time of biopsy were identified. There were 71 DSA+ and 192 DSA- patients (Figure 1). Of the 71 DSA+ patients, 46 had biopsy diagnosis of acute AMR (n=9) or chronic AMR (n=37), and 25 had normal histopathology or minimal non-specific interstitial fibrosis/tubular atrophy (IFTA). Of the 192 DSA- patients, 50 patients with normal histology and/or mild non-specific IFTA were used as a control group. Clinical and histopathological findings of these 3 groups (DSA+/AMR+, DSA+/AMR- and DSA-) were analyzed. A subgroup of patients who were enrolled in the Institutional Review Board-approved âImmune Monitoring Studyâ who had clinically indicated biopsy (n=61) and whole blood samples (n=54) stored were used for genomic analysis. Twenty-eight biopsy and blood samples from DSA+/AMR+ patients, 13 biopsy and 14 blood samples from DSA+/AMR- patients, and 20 biopsy and 12 blood samples from DSA- patients, were available for microarray analysis.
2013-08-23 | E-GEOD-50084 | biostudies-arrayexpress
Project description:Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) has been shown to have anti-inflammatory effects such as decreased growth factors and cytokines in animal models, this effect however, has not been investigated in kidney transplant recipients. We aimed to study the effect of ACEI or ARB treatment on intragraft gene expression profiles of transplant kidney biopsies using microarrays. Both groups had similar demographic characteristics in terms of age, race, sex, type of transplant, previous history of transplantation or acute rejection, panel reactive antibody levels, and immunosuppressive treatment. There were no differences in acute and chronic Banff allograft injury scores between the 2 Groups. Intragraft gene expression profiles of ACEI or ARB treated Group 2 biopsies showed decreased gene transcripts of interferon-gamma and rejection-associated transcripts (GRIT) and constitutive macrophage-associated transcripts (CMAT) compared to Group 1 biopsies. There were no statistically significant differences in expression of cytotoxic T cell (CAT), regulatory T cell (TREG), B-cell (BAT), natural killer cell (NKAT), or endothelial cell-associated transcripts (ENDAT) between the 2 Groups. Our data suggest that exposure to ACEI or ARB was associated with down-regulation of GRIT and CMAT. This anti-inflammatory effect of ACEI or ARB treatment could be an additional benefit in kidney transplant recipients. We identified 29 near normal biopsies with chronic sum allograft injury score (ct+ci+cv) ⤠3 for gene expression profiling comparing 2 groups; Group 1 (n=16), patients with no exposure of ACEI or ARB treatment and Group 2 patients (n=13) with exposure to ACEI or ARB at least 6 months prior to kidney biopsy. Biopsies with a diagnosis of acute or chronic rejection, recurrent or de novo glomerular disease, or polyoma nephropathy were excluded.
2016-06-10 | E-GEOD-83095 | biostudies-arrayexpress
Project description:Our understanding on mechanisms of ischemia-reperfusion induced lung injury during lung preservation and transplantation is based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic time (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with serum containing culture medium to similar lung transplantation. Cell morphology, viability and transcriptomic profiles were studied. Ischemia-reperfusion induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effects on these phenotypic characteristics. After CIT 18 h, protein biosynthesis related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene cluster in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell type dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
2021-04-17 | GSE172222 | GEO
Project description:Transcription factors (TFs) can relay signals through temporal alterations in their levels. The cell stress responsive TF p53 exhibits different dynamics depending on the type of stress, which influence the magnitude and dynamics of expression of its target genes and subsequent cellular outcomes. The mechanisms decoding p53 dynamics into levels and dynamics of RNA and protein of its targets remain unclear. We systematically quantified p53 target mRNA and protein levels over time under two p53 dynamical regimes – oscillatory and sustained – using RNA-seq and quantitative mass spectrometry. We categorized the mRNA dynamical patterns arising from oscillatory or sustained p53 expression, as well as the corresponding protein dynamics. We found that in both cases oscillatory dynamics allowed for the greatest variety of dynamical patterns of the downstream species. Target proteins from a wide range of functional categories were induced under both p53 dynamic conditions, with induction levels being overall higher under sustained dynamics. Mathematical modeling combined with analysis of empirical data revealed three mechanisms of decoding p53 dynamics: adjustment of mRNA and protein degradation rates, adjustment of activation thresholds for expression of mRNA and corresponding protein levels, and usage of coherent and incoherent feed-forward loop motifs in generating exclusive responses to p53 oscillatory or sustained dynamics, respectively. Our results highlight the diversity of mechanisms that decode complex TF dynamics into dynamical patterns of mRNA and proteins.
2022-02-11 | PXD027030 | Pride
Project description:The Immunoscore is a method to quantify the immune cell infiltration within cancers to predict the disease prognosis. Previous immune profiling approaches relied on limited immune markers to establish patients’ tumor immunity. However, immune cells exhibit a higher-level complexity that is typically not obtained by the conventional immunohistochemistry methods. Herein, we present a spatially variant immune infiltration score, termed as SpatialVizScore, to quantify immune cells infiltration within lung tumor samples using multiplex protein imaging data. Imaging mass cytometry (IMC) was used to target 26 markers in tumors to identify stromal, immune, and cancer cell states within 26 human tissues from lung cancer patients. Unsupervised clustering methods dissected the spatial infiltration of cells in tissue using the high-dimensional analysis of 16 immune markers and other cancer and stroma enriched labels to profile alterations in the tumors’ immune infiltration patterns. Spatially resolved maps of distinct tumors determined the spatial proximity and neighborhoods of immune-cancer cell pairs. These SpatialVizScore maps provided a ranking of patients’ tumors consisting of immune inflamed, immune suppressed, and immune cold states, demonstrating the tumor’s immune continuum assigned to three distinct infiltration score ranges. Several inflammatory and suppressive immune markers were used to establish the cell-based scoring schemes at the single-cell and pixel-level, depicting the cellular spectra in diverse lung tissues. Thus, SpatialVizScore is an emerging quantitative method to deeply study tumor immunology in cancer tissues.
2022-10-14 | PXD035340 | Pride