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Molecular characterization of acute cellular rejection occurring during intentional immunosuppression withdrawal in liver transplantation.
Am. J. Transplant. 16, 484-496 (2016)
Publ. Version/Full Text
DOI
PMC
Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period, its molecular phenotype is confounded by peri- and postoperative proinflammatory events. To unambiguously define the molecular profile associated with rejection, we collected sequential biological specimens from 55 patients at least 3 years after liver transplantation who developed rejection during trials of intentional immunosuppression withdrawal. We analyzed liver tissue and blood samples obtained before initiation of drug withdrawal and at rejection, alongside blood samples collected during the weaning process. Gene expression profiling was conducted using whole-genome microarrays and real-time polymerase chain reaction. Rejection resulted in distinct blood and liver tissue transcriptional changes in patients who were either positive or negative for hepatitis C virus (HCV). Gene expression changes were mostly independent from pharmacological immunosuppression, and their magnitude correlated with severity of histological damage. Differential expression of a subset of genes overlapped across all conditions. These were used to define a blood predictive model that accurately identified rejection in HCV-negative, but not HCV-positive, patients. Changes were detectable 1-2 mo before rejection was diagnosed. Our results provide insight into the molecular processes underlying acute cellular rejection in liver transplantation and help clarify the potential utility and limitations of transcriptional biomarkers in this setting.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Basic (laboratory) Research/science ; Clinical Research/practice ; Genomics ; Liver Allograft Function/dysfunction ; Liver Transplantation/hepatology ; Molecular Biology ; Rejection: Acute; Human Kidney-transplants; Allograft-rejection; Gene-expression; Mediated Rejection; T-cells; Transcripts; Tolerance; Biopsies; Tacrolimus; Antibodies
ISSN (print) / ISBN
1600-6135
e-ISSN
1600-6143
Quellenangaben
Volume: 16,
Issue: 2,
Pages: 484-496
Publisher
Wiley
Publishing Place
Hoboken, NJ
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Virology (VIRO)