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

Abstract

BackgroundThe 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.MethodsOne 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.ResultsHomozygous 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.ConclusionsThis 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.

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

“…They also showed a positive relationship between AR and the number of C2 group HLA alleles. Nevertheless, KIR genotypes and the number of KIR activating/inhibiting KIRs were not related to the allograft outcome and did not have a statistically significant effect on graft survival [ 74 ]. Legaz et al reported that KIR2DL3 and KIR2DS1 in recipients correlated with the increased incidence of AR in the presence of donor C2 ligands.…”

Determining the relevance of HLA/KIR matching/mismatching on kidney and liver transplantation rejection: A meta-analysis

“…The studies included were published as early as 2007 by Kreijveld et al (2007) and Kunert et al (2007), while the latest was published in 2017 by Jafari et al (2017) and Littera et al (2017). Most of the studies were done in western countries (Kreijveld et al 2007;Kunert et al 2007;La Manna et al 2013;Legaz et al 2013;Littera et al 2017) and only three were conducted in Asian countries (Alam et al 2015;Jafari et al 2017;Lee et al 2017). Among the eight studies included, two delved on liver transplantation rejection (Legaz et al 2013;Lee et al 2017).…”

“…Most of the studies were done in western countries (Kreijveld et al 2007;Kunert et al 2007;La Manna et al 2013;Legaz et al 2013;Littera et al 2017) and only three were conducted in Asian countries (Alam et al 2015;Jafari et al 2017;Lee et al 2017). Among the eight studies included, two delved on liver transplantation rejection (Legaz et al 2013;Lee et al 2017). Furthermore, La Manna et al (2013) and Littera et al (2017) focused on chronic types of rejection while the others involved acute graft rejection.…”

“…The degree of the contact between KIRs and HLA molecules controls whether activating or inhibitory signals are transmitted, which determines NK cell function (Tuttolomondo et al 2019). Several types of research have reported on NK cell KIRs and HLA/KIR combinations in solid organ transplantation, particularly the kidney and liver, but data is scarce and contradictory (Bishara et al 2005;Tran et al 2013;Jafari et al 2017;Lee et al 2017).…”

“…Research regarding the effect of the KIR receptors in recipients and HLA ligands in donor graft in determining the success rate of organ transplantation has been inconclusive. Some key studies including those from Kreijveld et al (2007), Kunert et al (2007), Lee et al (2017), did not find a correlation between HLA-KIR matching and allograft rejection. However, some studies such as in La Manna et al (2013), Legaz et al (2013), Alam et al (2015), Jafari et al (2017), andLittera et al (2017) were able to find some correlation between HLA/KIR matching and allograft rejection.…”