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MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE26622: MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Affymetrix) GSE26625: MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Illumina) Refer to individual Series

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PROVIDER: S-DIXA-D-1080 | biostudies-other |

REPOSITORIES: biostudies-other

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MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-01-09 | GSE26627 | GEO

MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS

Project description:This SuperSeries is composed of the following subset Series: GSE26622: MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Affymetrix) GSE26625: MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Illumina) Refer to individual Series

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MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Illumina)

Project description:In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation. The complete database comprised the expression measurements of 48766 probes in liver biopsies. The liver biopsy specimens available for the study were obtained: a) before immunosuppressive drugs were discontinued from tolerant (TOL, n=24) and non-tolerant (Non-TOL, n=29) recipients; b) at the time of rejection from non-tolerant recipients (Non TOL REJ, n=18); In addition, liver tissue samples were also collected from the following control patient groups: a) liver transplant recipients with chronic hepatitis due to recurrent hepatitis C virus infection (HEPC, n=12); b) liver transplant recipients with typical acute cellular rejection taking place during the immediate post-transplant period (REJ, n=9); c) liver transplant recipients under maintenance immunosuppression with normal liver function and normal liver histology 1 year after transplantation (CONT-Tx, n=8); and d) non-transplanted patients undergoing surgery for colorectal liver metastases (CONT, n=10).

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Gene expression in tolerant and non-tolerant liver allografts

Project description:Liver biopsy samples were obtained as part of the LITMUS trial (ClinicalTrials.gov NCT02541916). All samples were obtained from liver transplant recipients prior to immunosuppression withdrawal. Percutaneous liver biopsies were performed under local anaesthesia using an 18-gauge Jamshidi needle. A 0.5cm portion of the biopsy to be used for gene expression was stored in RNAlater (Qiagen) for 24 hours at 4 °C and then transferred to -80 °C. Specimens were thawed and transferred to a clean, RNase free microcentrifuge tube. Tissue samples were incubated in 600 ul of lysis buffer (Ambion) with 6 ul of 2-mercaptoethanol for 10 minutes. Tissue samples were then homogenized using a nuclease-free disposable pellet pestle (Kimble Kontes) and processed using the PureLink RNA Mini Kit (Ambion). RNA quality was evaluated using an Bioanalyzer 2100 (Agilent) and samples with RIN > 7 were submitted for sequencing and analysis at The Center for Applied Genomics (Toronto, Canada).

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