Mechanism of cellular and humoral rejection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE74261 | GEO | 2018/10/16
REPOSITORIES: GEO
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Project description:Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects. To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (LR) interactions.Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions. Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.
2023-03-28 | GSE228300 | GEO
Project description:Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period its molecular phenotype is confounded by pro-inflammatory events elicited by surgery, ischemia-reperfusion injury and early post-transplant complications. To unambiguously define the molecular profile associated with rejection we collected sequential biological specimens from liver transplant patients at least 3 years after transplantation who developed rejection while enrolled in trials of intentional immunosuppression withdrawal Transcriptomic RISET 2.0 chips were employed using portal blood vein from 37 liver trasplant patients.Two timepoints were selected: before immunosupressive weaning and rejection time point.
2016-06-01 | E-GEOD-70305 | biostudies-arrayexpress
Project description:Background: The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in transcriptomics on graft biopsies when extracorporeal photopheresis was used to treat chronic humoral rejection after kidney transplantation. Methods: we retrospectively analyzed the mRNA expression of 770 genes of interest in graft biopsies performed before and after treatment. Eight patients received an average of 23 extracorporeal photopheresis sessions over 4 months between the two biopsies. Results: Transcriptomic analysis of the graft biopsies identified a significant (adjusted p-value< 0.05) increase in CAV1 mRNA in all patients and a significant decrease in CD19, IL21, PAX5, and SFTPA2 mRNAs in 7 of 8 patients. Conclusions: In patients treated with extracorporeal photopheresis for chronic humoral rejection after renal transplantation, omic analysis of repeated biopsies shows a reduction in fibrotic and inflammatory transcriptomic signatures.
2024-02-28 | GSE240778 | GEO
Project description:Rhipicephalus microplushemocyte innate cellular and humoral immune responses to babesialinfection
| PRJNA1018599 | ENA
Project description:Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period its molecular phenotype is confounded by pro-inflammatory events elicited by surgery, ischemia-reperfusion injury and early post-transplant complications. To unambiguously define the molecular profile associated with rejection we collected sequential biological specimens from liver transplant patients at least 3 years after transplantation who developed rejection while enrolled in trials of intentional immunosuppression withdrawal
2016-06-01 | GSE70305 | GEO
Project description:Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single cell RNA and T cell receptor sequencing on recipient derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with acute cellular rejection and compare them with T cells obtained from the same three patients after clinical treatment of rejection with high-dose, systemic glucocorticoids. At the time of acute cellular rejection, we find an oligoclonal expansion of cytotoxic CD8+ T cells, that all persist as tissue resident memory T cells following successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators following therapy with glucocorticoids. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in-situ expansion. These findings pose a potential biological mechanism linking acute cellular rejection to chronic allograft damage.
2021-10-15 | GSE185659 | GEO
Project description:Transplant glomerulopathy (TGP) is frequently found in the setting of chronic antibody mediated rejection along with microvascular inflammation (MVI) (peritubular capillaritis+glomerulitis score > 1) and/or positive c4d staining. We assessed the molecular profiles of TGP in the absence of microvascular inflammation and C4d staining as compared to TGP with positive MVI and/or C4d. Gene expression profiles of TGP in the absence of microvascular inflammation and C4d lack molecular features of antibody-mediated rejection but suggest chronic cellular rejection.
2017-01-17 | GSE93659 | GEO
Project description:Circulating anti-HLA donor-specific antibodies (HLA-DSA) are often absent in serum of kidney allograft recipients with biopsies demonstrating histology of antibody-mediated rejection (ABMRh). In this multicenter study, we aimed to elucidate whether the transcriptional profile of biopsies with HLA-DSA negative ABMRh can indicate an undetected humoral etiology, or whether HLA-DSA negative ABMRh should be considered as a distinct histomolecular entity.
2020-11-10 | GSE147089 | 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