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Postischemic Inflammatory Response in an Auxiliary Liver Graft Predicts Renal Graft Outcome in Sensitized Patients.

Journal article
Authors Madeleine Ingelsten
Alex Karlsson-Parra
Anna Björnson Granqvist
Johan Mölne
Michael Olausson
Börje Haraldsson
Jenny Nyström
Published in Transplantation
Volume 91
Issue 8
Pages 888-894
ISSN 1534-6080
Publication year 2011
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Pathology
Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 888-894
Language en
Links dx.doi.org/10.1097/TP.0b013e3182100...
Subject categories Medical and Health Sciences

Abstract

BACKGROUND.: The liver is considered a tolerogenic organ that favors the induction of peripheral tolerance and protects other organs from the same donor from rejection. This has been exploited in combined auxiliary liver-kidney transplantation, where a renal graft is transplanted against a positive crossmatch under the protection of a liver transplanted from the same donor. METHODS.: To elucidate mechanisms behind the liver protective effect, we studied early transcriptional changes of inflammatory mediators in the grafts during combined auxiliary liver-kidney transplantation using microarrays and real-time polymerase chain reaction. The results were correlated to clinical data. RESULTS.: Liver and kidney grafts both exhibited an upregulation of the leukocyte-recruiting chemokines CCL2, CCL3, and CCL4. Notably, liver grafts strongly upregulated CCL20, a dendritic cell, and T-cell recruiting chemokine. By comparing the gene expression in liver grafts with the clinical outcome, we found that 14 of 45 investigated inflammatory genes were expressed significantly higher in patients without early rejection when compared with those with early rejections. This included the above-mentioned chemokines and the T-cell-recruiting CX3CL1, NFKB1, and the tolerance-inducing gene indoleamine 2,3-dioxygenase. CONCLUSIONS.: In this study, the protective role of the liver was associated with a proinflammatory reaction within this organ after ischemia-reperfusion. In particular, we found an increased expression of leukocyte-recruiting chemokines in patients without rejection, indicating a protective role of host inflammatory cells infiltrating the auxiliary liver graft in presensitized patients. Second, gene expression profiling of transplant biopsies shortly after reperfusion predicted the risk of early rejection in these patients.

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