Ann Lab Med.  2017 Jan;37(1):45-52. 10.3343/alm.2017.37.1.45.

Human Leukocyte Antigen-C Genotype and Killer Immunoglobulin-like Receptor-Ligand Matching in Korean Living Donor Liver Transplantation

• Lee H
• Park KH
• Park HS
• Ryu JH
• Lim J
• Kim Y
• Na GH
• Kim DG
• Oh EJ

• KMID: 2373613
• DOI: http://doi.org/10.3343/alm.2017.37.1.45

Abstract

BACKGROUND
The interaction between killer immunoglobulin-like receptors (KIRs) and HLA class I regulates natural killer (NK) cell cytotoxicity and function. The impact of NK cell alloreactivity through KIR in liver transplantation remains unelucidated. Since the frequency of HLA-C and KIR genotypes show ethnic differences, we assessed the impact of HLA-C, KIR genotype, or KIR-ligand mismatch on the allograft outcome of Korean liver allografts.
METHODS
One hundred eighty-two living donor liver transplant patients were studied. Thirty-five patients (19.2%) had biopsy-confirmed acute rejection (AR), and eighteen (9.9%) had graft failure. The HLA-C compatibility, KIR genotypes, ligand-ligand, and KIR-ligand matching was retrospectively investigated for association with allograft outcomes.
RESULTS
Homozygous C1 ligands were predominant in both patients and donors, and frequency of the HLA-C2 allele in Koreans was lower than that in other ethnic groups. Despite the significantly lower frequency of the HLA-C2 genotype in Koreans, donors with at least one HLA-C2 allele showed higher rates of AR than donors with no HLA-C2 alleles (29.2% vs 15.7%, P=0.0423). Although KIR genotypes also showed ethnic differences, KIR genotypes and the number of activating KIR/inhibitory KIR were not associated with the allograft outcome. KIR-ligand mismatch was expected in 31.6% of Korean liver transplants and had no impact on AR or graft survival.
CONCLUSIONS
This study could not confirm the clinical impact of KIR genotypes and KIR-ligand mismatch. However, we demonstrated that the presence of HLA-C2 allele in the donor influenced AR of Korean liver allografts.

Keyword

Killer immunoglobulin-like receptors; HLA-C; KIR-ligand mismatch; Liver transplantation; Allograft outcome

MeSH Terms

Adult
Alleles
Asian Continental Ancestry Group/*genetics
Female
Genotype
Graft Rejection
Graft Survival
HLA-C Antigens/*genetics
Homozygote
Humans
Killer Cells, Natural/cytology/immunology
Ligands
*Liver Transplantation
Male
Middle Aged
Proportional Hazards Models
Receptors, KIR/chemistry/*genetics/metabolism
Republic of Korea
Tissue Donors
Transplantation, Homologous
HLA-C Antigens
Ligands
Receptors, KIR

Figure

• 

  Fig. 1 Data represent the incidence of acute rejection (AR) in living donor liver transplant patients according to the donor HLA-C groups. (A) The incidence of AR increased as the number of HLA-C2 alleles increased (chi-square for trend 4.636, P=0.0313). (B) The AR incidence in patients with and without a donor HLA-C2 allele showed a statistically significant difference (P=0.0423).

• 

  Fig. 2 Comparison of graft survival (A) and patient survival (B) between HLA-C2 allele negative and HLA-C2 allele positive donors showed no significant difference.

• 

  Fig. 3 (A) KIR gene distribution with or without acute rejection. (B) KIR genotype patterns in patients with acute rejection and the total population.Abbreviation: KIR, killer immunoglobulin-like receptor.

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