Mechanism of cellular rejection in transplantation.
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ABSTRACT:
SUBMITTER: Ingulli E
PROVIDER: S-EPMC2778785 | biostudies-other | 2010 Jan
REPOSITORIES: biostudies-other
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Project description:Acute cellular rejection (ACR) is a common complication following lung transplantation (LTx), affecting almost a third of recipients in the first year. Established, comprehensive diagnostic criteria exist but they necessitate allograft biopsies which in turn increases clinical risk and can pose certain logistical and economic problems in service delivery. Undermining these challenges further, are known problems with inter-observer interpretation of biopsies and uncertainty as to the long-term implications of milder or indeed asymptomatic episodes. Increased risk of chronic lung allograft dysfunction (CLAD) has long been considered the most significant consequence of ACR. Consensus is lacking as to whether this applies to mild ACR, with contradictory evidence available. Given these issues, research into alternative, minimal or non-invasive biomarkers represents the main focus of research in ACR. A number of potential markers have been proposed, but none to date have demonstrated adequate sensitivity and specificity to allow translation from bench to bedside.
| S-EPMC7186718 | biostudies-literature
Project description:This study used RNAseq to study the mechanism of cellular and humoral rejection by comparing clinical samples of cellular, humoral, mixed, and normal.
2018-10-16 | GSE74261 | GEO
Project description:BackgroundInterleukin-28 (IL-28B) rs12979860 C/T polymorphism is a known predictor of sustained virological response after antiviral treatment in hepatitis C. IL-28B affects the innate immune system as well as intrahepatic expression level of interferon-stimulated genes.ObjectiveTo investigate the effect of recipient IL-28B polymorphism on occurrence of acute rejection after liver transplantation.Methods140 liver allograft recipients were selected. Acute rejection episodes were recorded in 39 patients (AR group); the remaining had normal graft function (non-AR group). 70 normal subjects were also studied as the control group. The IL-28B rs12979860 was genotyped through PCR-RFLP method.ResultsNo significant difference was found between AR and non-AR groups in terms of genotype and allele frequency. However, the CC genotype was significantly (p<0.001) more frequent in patients than in the control group; the C allele variants increased the risk of end-stage liver disease (OR: 2.60).ConclusionLiver damage in association with the carriage of IL-28B C allele is associated with a higher likelihood of developing cirrhosis.
| S-EPMC5347403 | biostudies-literature
Project description:BackgroundThe current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR.MethodsA total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7-427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5-17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis.ResultsTCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7.ConclusionPatients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor.
| S-EPMC9857115 | biostudies-literature
Project description: Not available
| S-DIXA-D-1015 | biostudies-other
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:Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.
| S-EPMC10514359 | biostudies-literature
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:BackgroundAcute cellular rejection (ACR) is one of the main factors in transplanted organ failure in liver transplantation. A precise marker for diagnosing or predicting rejection is not currently available; therefore, invasive liver biopsy is standard procedure. To develop a noninvasive method for precise diagnosis of ACR, we evaluated autoantibodies from patient sera as potential biomarkers using protein microarrays (seromics).MethodsSera from hepatitis C virus-positive ACR patients were compared to three hepatitis C virus cirrhosis control groups and healthy volunteers. The control groups consisted of 2 no-ACR groups obtained on postoperative day 28 and 1 year after transplantation and a preoperative group obtained 1 day before transplantation. For validation, we evaluated whether the candidate antibodies can distinguish ACR from other types of liver dysfunction after liver transplantation using enzyme-linked immunosorbent assay.ResultsSeromic analysis by weighted average difference (WAD) ranking and Mann-Whitney U test revealed a significant increase of 57 autoantibodies in the sera of ACR patients with liver dysfunction. Among the 57 candidates, autoantibodies to charged multivesicular body protein 2B, potassium channel tetramerization domain containing 14, voltage gated subfamily A regulatory beta subunit 3, and triosephosphate isomerase 1 were regarded as potential biomarkers of ACR after liver transplantation. Using 20 ACR patients with variable backgrounds for validation, the autoantibodies to charged multivesicular body protein 2B and triosephosphate isomerase 1 were significantly increased in ACR patients compared to other control groups.ConclusionsA panel of autoantibodies identified by seromics as potential noninvasive biomarkers was clinically useful for diagnosing ACR after liver transplantation.
| S-EPMC5142373 | biostudies-literature
Project description:BackgroundPharmaceuticals to inhibit mammalian target of rapamycin (mTOR) protein, which plays an integral role in T cell survival and function, have been used to prevent complications associated with organ transplantation. Although studies have individually shown that resveratrol can inhibit mTOR and that inhibiting mTOR leads to attenuated immune function, no studies to date have examined these two functions conjointly under one study. Therefore, we hypothesize that resveratrol will decrease mTOR activation and expression as well as attenuate stimulated T cell activation and proliferation in peripheral blood mononuclear cells (PBMC).Methods and materialsHuman PBMC were isolated and cultured. The cells were pre-treated with resveratrol (50 μM) overnight (18 hrs) before stimulation. The cells were collected for subsequent biochemical analysis after 1, 3, and 5 days. Additionally, the cells were stained with proliferation dye and cultured for 24 hours in PMA/Ionomycin with resveratrol for flow cytometry analysis.ResultsResveratrol treated stimulated PBMCs displayed a significant decrease in activated phosphorylation of mTOR at days 1, 3, and 5 (P < 0.0329). Markers of T cell activation, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), were also significantly reduced along with T cell proliferation following stimulated PBMC resveratrol treatment when compared to vehicle-treated controls (P < 0.01).ConclusionTaken together, our data suggest that resveratrol can decrease the immune response of stimulated T-cells and inhibit the expression and activation of mTOR mediated cellular signalling under the same study setting. Therefore, resveratrol proposes a possible adjunctive therapy option for patients undergoing organ transplantation.
| S-EPMC7811925 | biostudies-literature