期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 8, 期 9, 页码 1931-1941出版社
WILEY
DOI: 10.1111/j.1600-6143.2008.02341.x
关键词
chronic rejection; graft cirrhosis; graft survival; HLA-C1 genotype; HLA-C2 genotype; KIR; liver transplantation; NK cells; patient survival
资金
- Department of Histocompatibility and Immunogenetics at the National Blood Service Centre
- The Medical School, University of Birmingham
- University Hospital Birmingham, Birmingham, UK
- Howard Ostin Research Funds
- Medical Research Council [G9818340B] Funding Source: researchfish
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.
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