2011 - Transplantomics and Biomarkers in Transplantation


This page contains exclusive content for the member of the following sections: TTS. Log in to view.

Abstract Driven Session

9.2 - Microarray gene expression profiling of acute liver allograft rejection

Presenter: Marta, Lopez, Barceona, Spain
Authors: Marta Lopez, Carlos Benitez, Juan Jose Lozano, Marc Martinez-Llordella, Maria Londoño, Stefan Tomiuk, Uwe Janssen, Jacques Pirenne, Tommaso Manzia, Antonio Rimola, Giuseppe Tisone, Alberto Sanchez-Fueyo

Microarray gene expression profiling of acute liver allograft rejection

Marta Lopez1, Carlos Benitez1, Juan Jose Lozano1, Marc Martinez-Llordella1, Maria Londoño1, Stefan Tomiuk2, Uwe Janssen2, Jacques Pirenne3, Tommaso Manzia4, Antonio Rimola1, Giuseppe Tisone4, Alberto Sanchez-Fueyo1.
1Liver Transplant Unit, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barceona, Spain; 2Miltenyi Biotec, Germany; 3University Hospitals Leuven, Belgium; 4University Tor Vergata Rome, Italy.

Introduction: In contrast to other transplantation settings, the molecular characteristics of acute cellular rejection in human liver transplantation have not been adequately defined. In order to simultaneously assess the peripheral blood and liver tissue molecular profile of liver recipients undergoing acute rejection, we sequentially collected biological samples from recipients enrolled in a prospective multicenter European immunosuppression withdrawal clinical trial and conducted microarray gene expression profiling.

Methods: 96 liver recipients (>3 years after tx) were enrolled in the trial. Immunosuppression was gradually discontinued over a 6-9 month: the procedure was successful in 40 patients, while the remaining 56 recipients rejected during weaning. In rejecting patients RNA was extracted from liver biopsies obtained at baseline and at the time of rejection and processed on Illumina whole-genome expressionmicroarrays.In addition, RNAs obtained from sequential whole blood samples were hybridized onto the custom RISET 2.0 microarray (Agilent oligonucleotide microarray comprising 5,069 transplant-relevant probes).

Results: Rejection was associated with significant changes in the expression of 330 genes in liver tissue and 164 genes in blood (FDR<5%). Rejecting grafts exhibited an exuberant inflammatory response characterized by the upregulation of chemokines (CXCL10, CXCL9), cytokines (IL32, IL8), immune-activation markers (CD44, CD83, Stat1, CD69, CTLA4) and cytotoxicity-relates molecules (PRF1, GZMA, CD8A, CD3D). In contrast, blood expression changes were smaller in their magnitude and mainly characterized by up- and down-regulation of metabolism-related genes, with minor contribution from immunostimulatory genes. Some overlaps between blood and tissue were however noted, namely CXCL10, CD74, CDC20, CCNB2, HLA-DMB.

Conclusions: In liver transplantation acute rejection is associated with significant, but only minimally overlapping, gene expression changes in liver tissue and in blood. The specificity of liver allografts should be taken into account when employing transcriptional biomarkers developed in other transplantation settings.


Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.

Social

Contact

Staff Directory
+1-514-874-1717
info@tts.org

Address

The Transplantation Society
International Headquarters
740 Notre-Dame Ouest
Suite 1245
Montréal, QC, H3C 3X6
Canada