title: Postischemic inflammatory response in an auxiliary liver graft predicts renal graft outcome in sensitized patients.
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.
authors.affiliation: Department of Clinical and Molecular Medicine (Nephrology), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Madeleine.ingelsten@microbio.gu.se
authors.forename: Madeleine
authors.initials: M
authors.lastname: Ingelsten
authors.forename: Alex
authors.initials: A
authors.lastname: Karlsson-Parra
authors.forename: Anna Björnson
authors.initials: AB
authors.lastname: Granqvist
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.forename: Michael
authors.initials: M
authors.lastname: Olausson
authors.forename: Börje
authors.initials: B
authors.lastname: Haraldsson
authors.forename: Jenny
authors.initials: J
authors.lastname: Nyström
mesh_terms: D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000097:blood; D001706:Biopsy; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006648:Histocompatibility; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D007511:Ischemia / Q000235:genetics / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018570:Risk Assessment; D013548:Sweden; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D018925:Chemokines; D018836:Inflammation Mediators; D012333:RNA, Messenger