Intrahepatic immune microenvironment contributes to spontaneous tolerance in pediatric liver transplantation recipients
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ABSTRACT:
PROVIDER: PRJNA1011976 | ENA |
REPOSITORIES: ENA
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Project description:We carried out a cross-sectional study using clinical data and biospecimens to analyze factors that were associated with immune tolerance after pediatric liver transplantation. Multivariable analysis revealed that peripheral Treg ratio (OR=2.48 (1.55-19.8), p=0.032) and maximum blood EBV-DNA copy (OR=5.53 (1.08-5.67), p=0.008) were associated with the development of tolerance during follow-up, while serum IGM titer (OR=0.73 (0.53-0.99), p=0.046) had a negative relation with tolerance. Histological evaluation indicated no difference on hepatocyte damage, portal inflammation and fibrosis stage between tolerant and non-tolerant recipients. Meanwhile, no deterioration of hepatic pathology was found in recipients with longer follow-up time. Further allograft biopsy transcriptome analysis exhibited distinguished intrahepatic expression patterns between tolerant and non-tolerant recipients. Tolerant allografts were characterized by low expression of cytotoxic and inflammatory genes (like NDUFAF2, MAN1A2, PLEK2, NUDFB4 and FCER1G) and high levels of immune regulatory ones (like SCRIB, MAPK8IP3, TSC2, CHRNA4 and D2HGDH). Especially, immunohistology staining confirmed the upregulated expression of CD39 (ENTPD1) and CD73 (NT5E) in liver sinusoidal endothelial cells and hepatocytes from tolerant allograft, which was associated with increased CD4+ Treg ratio in portal areas.
2024-05-01 | GSE242205 | GEO
Project description:Approximately 2% of heathy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood-borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. We examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and hepatectomy patients and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 hepatectomy patients who received care at the Kyusyu University Hospital between May 1997 and September 2017. Total RNA was extracted from peripheral blood samples of patients/recipients collected postoperatively. HPgV RNA was measured using real-time polymerase chain reaction (RT-PCR). Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and two patients (1.1%) had HPgV viremia. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion as HPgV RNA was detected from the blood bag transfused to the recipient during LT. Additionally, HPgV infection induced the upregulation of interferon stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs). LT recipients had higher HPgV viremia compared to hepatectomy patients. Although HPgV infection was not associated with LT-related outcomes, it induced ISG expression in recipients.
2019-07-28 | GSE131504 | GEO
Project description:mmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as ‘operationally’ tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter ‘fingerprint’ of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for ?d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+CD25+ T-cells and Vd1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.
2008-06-25 | GSE11881 | GEO
Project description:The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation. Two centers data was included, which are 41 samples from Stanford as the training set and 44 samples from UCLA as the test set. 26 samples from Stanford and 15 samples from UCLA were used in microarray Agilent whole human genome microarray
2012-02-01 | E-GEOD-30886 | biostudies-arrayexpress
Project description:The sensitization of patients to human leukocyte antigens prior to heart transplantation is increasingly being recognized as an important challenge both before and after the transplant, and the effects of sensitization on clinical outcomes are just beginning to be understood. Many patients are listed with the requirement of a negative prospective or virtual crossmatch prior to accepting a donor organ. This strategy has been associated with both longer waitlist times and higher waitlist mortality. An alternative approach is to transplant across a potentially positive crossmatch while utilizing strategies to decrease the significance of the human leukocyte antigen antibodies. This review will examine the challenges and the impact of sensitization on pediatric patients prior to and following heart transplantation.
| S-EPMC3884159 | biostudies-other
Project description:The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation.
2012-02-01 | GSE30886 | GEO
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
2009-08-05 | GSE13440 | GEO
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:Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival after kidney transplantation. We previously showed that tolerance could be induced and full donor chimerism, as well as immunosuppression withdrawal, was obtained in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Gene expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection were compared. This dataset is part of the TransQST collection.
2018-05-07 | E-GEOD-106675 | biostudies-arrayexpress