Impact of Recipient HLA-C in Liver Transplant: A Protective Effect of HLA-Cw*07 on Acute Rejection

Moya‐Quiles, María Rosa; Alvarez, Ruben; Miras, M.; Gómez-Mateo, Jorge; Marin-Moreno, Isabel; Martínez‐Barba, Enrique; Sanchez-Mozo, Maria P.S.; Gómez, Manuel; Arnal, F; Sánchez‐Bueno, Francisco; Marı́n, Luis; García‐Alonso, Ana M.; Minguela, Alfredo; Muro, Manuel; Parrilla, Pascual; Alonso, Clara; Álvarez-López, María R.

doi:10.1016/j.humimm.2006.10.009

Cited by 24 publications

(22 citation statements)

References 41 publications

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“…There have been conflicting reports on the impact of KIR genes and KIR-ligand matching in LT [910111213]. KIR-ligand mismatches might induce recipient NK alloreactivity toward the liver allograft, resulting in a negative effect on the graft.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies utilized several KIR models such as KIR gene-gene mismatch, HLA-C genotype mismatch, and KIR-ligand mismatch for donors lacking ligands for inhibitory KIR, which present in recipients [589]. In liver transplantation (LT), previous studies reported the impact of HLA-C allotypes on acute rejection (AR) and graft survival [910111213], but some studies demonstrated no effect on graft outcomes [14]. In addition, most previous studies for HLA-C, KIR genotypes, or KIR-ligand matching in LT do not report Asians as a separate group, and no data has been acquired previously for Korean liver transplants.…”

Section: Introductionmentioning

confidence: 99%

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

Lee

Park

et al. 2017

Ann Lab Med

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lee

Park

et al. 2017

Ann Lab Med

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“…The HLA-C alleles were assigned to the 2 major KIR-ligand groups, C1 and C2, as previously reported [39,40].…”

Section: Hla-c Genotypingmentioning

confidence: 99%

Divergences in KIR2D+ natural killer and KIR2D+CD8+ T-cell reconstitution following liver transplantation

et al. 2011

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“…KIR2DL2/3 proteins bind HLA-C alleles carrying an asparagine at position 80 while KIR2DL1 recognizes HLA-C alleles with a lysine at this position. These two HLA-C types are termed group 1 (HLA-C1) and group 2 (HLA-C2), respectively (19), and all HLA-C allotypes ( (22,23), neoplastic (24) and infectious diseases (20), as well as outcome following hematopoietic stem cell transplantation (25 (26); whereas for liver transplants an association with acute rejection has been observed (27,28 (Figure 2A). Figure 2C) but no effect was seen on the development of hepatic artery thrombosis ( Figure 2D).…”

Section: In Terms Of Specificity There Are Two Main Groups Of Kirs mentioning

confidence: 99%

Donor HLA-C Genotype Has a Profound Impact on the Clinical Outcome Following Liver Transplantation

Hanvesakul

Spencer

Cook

et al. 2008

American Journal of Transplantation

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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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Impact of Recipient HLA-C in Liver Transplant: A Protective Effect of HLA-Cw*07 on Acute Rejection

Cited by 24 publications

References 41 publications

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

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

Divergences in KIR2D+ natural killer and KIR2D+CD8+ T-cell reconstitution following liver transplantation

Donor HLA-C Genotype Has a Profound Impact on the Clinical Outcome Following Liver Transplantation

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