Bonaccorsi-Riani, E.* ; Pennycuick, A.* ; Londoño, M.C.* ; Lozano, J.J.* ; Benítez, C.* ; Sawitzki, B.* ; Martínez-Picola, M.* ; Bohne, F. ; Martínez-Llordella, M.* ; Miquel, R.* ; Rimola, A.* ; Sánchez-Fueyo, A.*
Molecular characterization of acute cellular rejection occurring during intentional immunosuppression withdrawal in liver transplantation.
Am. J. Transplant. 16, 484-496 (2016)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2016
Prepublished im Jahr
2015
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
1600-6135
e-ISSN
1600-6143
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 16,
Heft: 2,
Seiten: 484-496
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Wiley
Verlagsort
Hoboken, NJ
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Immune Response and Infection
PSP-Element(e)
G-502700-002
Förderungen
Copyright
Erfassungsdatum
2015-12-08