Donor HLA-C genotype has a profound impact on the clinical outcome following liver transplantation

Rajesh Hanvesakul, N Spencer, Mark Cook, Bridget Gunson, M Hathaway, R Brown, P Nightingale, Paul Cockwell, Stefan Hubscher, David Adams, Paul Moss, Dennis Briggs

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Late allograft dysfunction is a significant problem following liver transplantation and its pathogenesis is uncertain. HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that regulate the cytotoxic activity of natural killer (NK) cells. HLA-C alleles can be allocated into two groups, termed HLA-C1 and HLA-C2, based on their KIR specificity. HLA-C2 interactions are more inhibiting to NK cell activation. We studied the clinical importance of HLA-C genotype in a large liver transplant cohort and found that possession of at least one HLA-C2 allele by the donor allograft was associated with less histological evidence of chronic rejection and graft cirrhosis, a 16.2% reduction in graft loss (p = 0.003) (hazard ratio: 2.7, 95% CI 1.4-5.3) and a 13.6% improvement in patient survival (p = 0.01) (hazard ratio: 1.9, 95% CI 1.1-3.3) at 10 years. Transplantation of an HLA-C2 homozygous allograft led to a particularly striking 26.5% reduction in graft loss (p <0.001) (hazard ratio: 7.2, 95% CI 2.2-23.0) at 10 years when compared to HLA-C1 homozygous allografts. Donor HLA-C genotype is therefore a major determinant of clinical outcome after liver transplantation and reveals the importance of NK cells in chronic rejection and graft cirrhosis. Modulation of HLA-C and KIR interactions represents an important novel approach to promote long-term graft and patient survival.
Original languageEnglish
Pages (from-to)1931-41
Number of pages11
JournalJournal of Leukocyte Biology
Volume8
Issue number9
DOIs
Publication statusPublished - 1 Sep 2008

Keywords

  • HLA-C1 genotype
  • patient survival
  • liver transplantation
  • NK cells
  • graft survival
  • KIR
  • HLA-C2 genotype
  • chronic rejection
  • graft cirrhosis

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