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HLA-C Matching and Liver Transplants: Donor-Recipient Genotypes Influence Early Outcome and CD8(+)KIR2D(+) T-Cells Recuperation

  作者 Lopez-Alvarez, MR; Moya-Quiles, MR; Minguela, A; Gil, J; Miras, M; Campillo, JA; Diaz-Alderete, MA; Garcia-Alonso, AM; Sanchez-Bueno, F; Vicario, JL; Muro, M; Alvarez-Lopez, MR  
  选自 期刊  Transplantation;  卷期  2009年88-3;  页码  S54-S61  
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[摘要]Background. Fully human leukocyte antigens (HLA)-mismatched liver grafts are well accepted, but the HLA influence on acceptance or rejection is unclear and much less so the impact of HLA-C, which may be conditioned by the fact that HLA-C-encode molecules are the major ligands for killer cell immunoglobulin-like receptors (KIR).Methods. The HLA-C allele compatibility and the effect of donor and recipient HLA-C genotype on early liver graft acceptance and on CD8+KIR+ T-cells recuperation were analyzed in a series of 431 primary liver transplants. Standard polymerase chain reaction PCR-SSO was used for HLA-C typing and flow cytometry to identify T cells KIR positives. Transplants were classified into two groups: acute rejection and nonacute rejection, and individual HLA-C genotypes as C1/C1, C2/C2, and C1/C2.Results. A favorable effect of HLA-C allelic compatibility on early liver graft acceptance was found because acute rejection significantly increased in transplants performed with 2 HLA-C allele mismatches (P=0.02). Considering the HLA-C groups, it was observed that C1/C2 heterozygous donors were best accepted in C1/C1 patients than in C2/C2 recipients, who experienced a high rate of acute rejection (P<0.004 and P<0.005, respectively). In addition, after transplantation CD3(+)CD8(+)KIR2D(+) T-cells repertoires significantly increased in C1/C1 and C1/C2, but not in C2/C2 patients.Conclusions. This study confirms the benefit of HLA-C allele matching on early liver transplant outcome and shows that donor HLA-C heterozygosis influences the alloresponse of C1 and C2 homozygous patients and the recuperation of CD3(+)CD8(+)KIR2D(+) T cells, suggesting an involvement in liver graft tolerance.

 
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