Differential expression of Organ Transplant Rejection related genes after xenokidney from 1KO.1TG vs. 3KO.7TG donor pigs
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ABSTRACT:
ORGANISM(S): Homo sapiens Macaca mulatta
PROVIDER: GSE268633 | GEO | 2025/08/21
REPOSITORIES: GEO
Similar Datasets
Project description:Differential expression of Organ Transplant Rejection related genes after xenokidney from 1KO.1TG vs. 3KO.7TG donor pigs
| PRJNA1117941 | ENA
Project description:Introduction: Responses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elucidate signatures of kidney allograft rejection. Methods: DRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4+ and CD8+ DRTC were flow-sorted, and the TCR sequences were identified using Adaptive Immunosequencing. DRTC were then tracked in post-transplant biopsies, blood, and urine samples in a cohort of kidney transplant recipients. Results: In patients with an abnormal biopsy, the majority of CD8+ DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8+ DRTC were more abundant pre- and post-transplant in patients that received non-lymphodepletional induction and developed an abnormal biopsy when compared to stable patients. Additionally, DRTC were detected as early as two weeks post-transplant in the urine of some patients, with some of these clones subsequently identified in follow-up kidney biopsy samples. Discussion: The findings of our study add to our understanding of T-cell alloreactivity following kidney transplantation and provide evidence for the role of pre-defined alloreactive T-cells in the development of allograft rejection.
2025-02-10 | GSE288648 | GEO
Project description:BackgroundWe previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, a tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC (MHCI) antigen (DST-antibodies).MethodsWe examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. We also examined an anti-donor class II MHC (MHCII) antibody that recognizes donor DCs more selectively.ResultsPreoperative transfer of DST-antibodies or DST pretreatment eliminated all passenger leukocytes, including both DC subsets and depleted the sessile DCs in the graft to ~20% of control. The CD172a+CD11b/c+ immunogenic subset was almost abolished. The intrahost direct or semi-direct allorecognition pathway was successfully blocked, leading to a significant suppression of the CD8+ T-cell response in the recipient lymphoid organs and the graft with delayed graft rejection. Anti-donor MHCII antibody had similar effects without temporary graft damage. Although DST pretreatment had a priming effect on the proliferative response of recipient regulatory T cells, DST-primed sera and the anti-donor MHCII antibody did not.ConclusionDST-antibodies and anti-donor MHCII antibodies could suppress the CD8+ T-cell-mediated liver transplant rejection by depleting donor immunogenic DCs, blocking the direct or semi-direct pathways of allorecognition. Donor MHCII-specific antibodies may be applicable as a selective suppressant of anti-donor immunity for clinical liver transplantation without the cellular damage of donor MHCII- graft cells and recipient cells.
| S-EPMC8060989 | biostudies-literature
Project description:BackgroundElevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR.MethodsDonor-derived cell-free DNA was assayed in 90 blood samples with paired DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for diagnosis of active ABMR were determined for samples with prior or current positive DSA (DSA+, n = 33).ResultsThe median level of dd-cfDNA (2.9%) in DSA+ patients with active ABMR was significantly higher than the median level (0.34%) in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA- patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect active ABMR in DSA+ patients was 81%, whereas the negative predictive value was 83%. The positive predictive value for DSA+ alone was 48%.ConclusionsThe combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.
| S-EPMC6133406 | biostudies-literature
Project description:BackgroundDonor -specific HLA antibody (DSA) is present in many kidney transplant patients whose biopsies are classified as no rejection (NR). We explored whether in some NR kidneys DSA has subtle effects not currently being recognized.MethodsWe used microarrays to examine the relationship between standard-of-care DSA and rejection-related transcript increases in 1679 kidney transplant indication biopsies in the INTERCOMEX study (ClinicalTrials.gov NCT01299168), focusing on biopsies classified as NR by automatically assigned archetypal clustering. DSA testing results were available for 835 NR biopsies and were positive in 271 (32%).ResultsDSA positivity in NR biopsies was associated with mildly increased expression of antibody-mediated rejection (ABMR)-related transcripts, particularly IFNG-inducible and NK cell transcripts. We developed a machine learning DSA probability (DSAProb) classifier based on transcript expression in biopsies from DSA-positive versus DSA-negative patients, assigning scores using 10-fold cross-validation. This DSAProb classifier was very similar to a previously described "ABMR probability" classifier trained on histologic ABMR in transcript associations and prediction of molecular or histologic ABMR. Plotting the biopsies using Uniform Manifold Approximation and Projection revealed a gradient of increasing molecular ABMR-like transcript expression in NR biopsies, associated with increased DSA (P<2 × 10-16). In biopsies with no molecular or histologic rejection, increased DSAProb or ABMR probability scores were associated with increased risk of kidney failure over 3 years.ConclusionsMany biopsies currently considered to have no molecular or histologic rejection have mild increases in expression of ABMR-related transcripts, associated with increasing frequency of DSA. Thus, mild molecular ABMR-related pathology is more common than previously realized.
| S-EPMC8806080 | biostudies-literature
Project description:Animals responded to Cp40 treatment (Late Rejector) showed a distinct pattern of gene expression compared to animals who did not respond (Early Rejector).
2021-06-25 | GSE178843 | GEO
Project description: Not available
| S-EPMC6587949 | biostudies-literature
Project description:BackgroundStandard-of-care biomarkers for renal allograft rejection are lagging indicators, signaling existing organ injury. This precludes early intervention, when immunological cascades leading to rejection are most susceptible. Donor-derived cell-free DNA (dd-cfDNA) shows promise as an early indicator of rejection, allowing earlier and possibly more effective treatment. This analysis was designed to assess this promise using real-world dd-cfDNA testing evidence.MethodsThis retrospective analysis of the prospective, observational ProActive registry study (NCT04091984) assessed dd-cfDNA and serum creatinine levels before biopsy in 424 patients with ≥1 dd-cfDNA test (n = 1013) in the 6 mo before biopsy.ResultsOf 4667 enrolled patients, 1631 patients had ≥18 mo of follow-up data, of which 424 had a biopsy and were included in this analysis. Twenty-six biopsies showed antibody-mediated rejection (ABMR), 62 showed T cell-mediated rejection, and 336 showed nonrejection; each from a unique patient. dd-cfDNA fractions were significantly elevated 5 mo before ABMR biopsies, and 2 mo before T cell-mediated rejection biopsies, compared with nonrejection biopsies. In contrast, serum creatinine did not discriminate between rejection and nonrejection in advance, or concurrent with biopsy. Among patients with nonrejection biopsies, estimated glomerular filtration rate was significantly lower in cases with ≥2 increased dd-cfDNA results (≥1%), compared with those with 0 or 1 increased dd-cfDNA result.ConclusionsThese data indicate that dd-cfDNA is an early indicator of biopsy-proven rejection, especially ABMR, suggesting a greater role for dd-cfDNA in surveillance to identify patients at high risk of ongoing or future rejection, thus requiring closer monitoring, biopsy, or other management changes.
| S-EPMC11335081 | biostudies-literature
Project description:IntroductionAcute rejection is a significant risk factor for developing chronic lung allograft dysfunction. Current monitoring tools, transbronchial biopsies and HLA antibody determination, have limitations in detecting acute rejection. This study aims to explore the potential utility of donor-derived cell-free DNA (ddcfDNA) as a non-invasive biomarker for detecting acute rejection in lung transplant recipients (LTR).MethodsWe developed a molecular method based on digital droplet PCR to determine the total amount and the proportion of ddcfDNA. Using blood samples collected sequentially post-transplant from a cohort of 81 LTR, we compared median levels of %ddcfDNA in patients with acute cellular rejection (ACR), antibody-mediated rejection (AMR), infection, or decline in pulmonary function (FEV1).ResultsMedian %ddcfDNA levels were significantly higher in groups with ACR (1.92% [0.70%, 2.30%], p=0.0006), AMR (1.27% [0.34%, 2.29%], p=0.0009), isolated lymphocytic bronchiolitis (0.54% [0.23%, 2.18%], p=0.03), and infection or prolonged ventilation over 30 days (0.50% [0.22%, 2.35%], p=0.005) versus stable allograft function group (0.26% [0.09%, 0.60%]). %ddcfDNA levels were also elevated in patients with FEV1 loss compared to those with stable or improving FEV1 after 12 months (1.98% vs. 1.36%, p=0.04). An optimal cut-off of 0.73% for %ddcfDNA was calculated to detect ACR and AMR with 80% specificity and 68% sensitivity.Discussion%ddcfDNA is a promising biomarker for identifying allograft injury due to acute rejection in LTR and could be a valuable tool for monitoring allograft health.
| S-EPMC11814210 | biostudies-literature
Project description:Ulcerative Colitis fecal samples were transplanted into IL10 deficient gnotobiotic mice. Half of the mice received a protease inhibitor cocktail in their drinking water. After 8-weeks colonization the animals were studied for colonic inflammation, and fecal samples were collected and analyzed by LC-MS3 based quantitative metaproteomics. Data from mice transplanted with two UC patients were analyzed in this dataset.
2020-11-23 | MSV000086510 | MassIVE