J Korean Surg Soc.  2010 Jun;78(6):357-368. 10.4174/jkss.2010.78.6.357.

Recipient's Killer Cell Immunoglobulin-like Receptor Genotype and Human Leukocyte Antigen C Ligand Influence the Clinical Outcome following Living Donor Liver Transplantation

Affiliations
  • 1Department of Surgery, Daejeon St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Daejeon, Korea.
  • 2Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul, Korea. kimdg@catholic.ac.kr
  • 3Department of Microbiology, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul, Korea.
  • 4Hematopoietic Stem Cell Bank, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul, Korea.
  • 5Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul, Korea.

Abstract

PURPOSE
The design of this study was to determine the most influential factor(s) on post-transplant immunological consequences, particularly with regard to the role of killer cell immunoglobulin-like receptors (KIRs) and their ligands (type I human leukocyte antigen (HLA)) in unstable liver function.
METHODS
Retrospectively collected data from 319 recipients undergoing adult living donor liver transplantation (LDLT) using a right lobe graft between January 2002 and August 2008 were analyzed. Patients were categorized according to the serum alanine transaminase (ALT) pattern; stable ALT pattern was defined as ALT pattern during 3 months post-transplantation, except for initial 2 weeks post-transplantation, in which 2 times or less additional elevation(s) of serum alanine transaminase (ALT) (> or =80 IU/L) were observed. When a serum ALT pattern showed fluctuating and/or unpredictable nature, it was defined as an unstable pattern. In addition, genetic information of KIRs and HLA-C allotypes received from 68 recipients and 59 donors was analyzed by way of polymerase chain reaction using sequence-specific primers (PCR-SSP) to determine the factor(s) influencing a serum ALT pattern.
RESULTS
Among 319 LDLT recipients included in this study, the actual incidences of AR and unstable ALT pattern were 13.4% (43/319) and 42.3% (135/319), respectively. Unstable ALT pattern correlated with poorer survival following LDLT than stable pattern (P<0.000). Genetically, unstable ALT pattern was related to recipients carrying KIR2DL2(+)/KIR2DS2(+) combined with the heterogeneous HLA-C allotype (HLA-C1/C2), (relative risks 45.0, 95% confidence interval 2.160~937.321; P=0.013).
CONCLUSION
This study indicates that, when performing LDLT, pretransplant determination of recipient's KIRs and HLA-C allotypes may be beneficial in coping with post-transplant immunological circumstances.

Keyword

Killer immunoglobulin-like receptor (KIR); Human leukocyte antigen (HLA); Alanine transaminase (ALT); Living donor liver transplantation (LDLT); Natural killer cell (NK cell)

MeSH Terms

Adult
Alanine Transaminase
Genotype
HLA-C Antigens
Humans
Incidence
Leukocytes
Lifting
Ligands
Liver
Liver Transplantation
Living Donors
Polymerase Chain Reaction
Receptors, KIR
Retrospective Studies
Tissue Donors
Transplants
Alanine Transaminase
HLA-C Antigens
Ligands
Receptors, KIR

Figure

  • Fig. 1 Survival curves in each group stratified according to presence of acute rejection and serum ALT pattern and acute rejection. (A) Overall survival according to presence of acute rejection, (B) Overall survival according to serum ALT pattern.

  • Fig. 2 Distributions of stable/unstable pattern according to the recipient's HLA-C allotypes in patients with KIR2DL2(+)/KIR2DS2(+).


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