Killer Cell Immunoglobulin-like Receptors (KIR) and Human Leucocyte Antigen C (HLA-C) Increase the Risk of Long-Term Chronic Liver Graft Rejection

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Oct 27

PMID 36293011

Authors

Isabel Legaz

Jose Miguel Bolarin

Jose Antonio Campillo

Maria R Moya-Quiles

Manuel Miras

Manuel Muro

Alfredo Minguela

Maria R Alvarez-Lopez

Affiliations

Soon will be listed here.

Abstract

Chronic liver rejection (CR) represents a complex clinical situation because many patients do not respond to increased immunosuppression. Killer cell immunoglobulin-like receptors/Class I Human Leukocyte Antigens (KIR/HLA-I) interactions allow for predicting Natural Killer (NK) cell alloreactivity and influence the acute rejection of liver allograft. However, its meaning in CR liver graft remains controversial. KIR and HLA genotypes were studied in 513 liver transplants using sequence-specific oligonucleotides (PCR-SSO) methods. KIRs, human leucocyte antigen C (HLA-C) genotypes, KIR gene mismatches, and the KIR/HLA-ligand were analyzed and compared in overall transplants with CR (n = 35) and no-chronic rejection (NCR = 478). Activating KIR (aKIR) genes in recipients (rKIR2DS2 and rKIR2DS3) increased CR compared with NCR groups ( = 0.013 and = 0.038). The inhibitory KIR (iKIR) genes in recipients rKIR2DL2 significantly increased the CR rate compared with their absence (9.1% vs. 3.7%, = 0.020). KIR2DL3 significantly increases CR (13.1% vs. 5.2%; = 0.008). There was no influence on NCR. CR was observed in HLA-I mismatches (MM). The absence of donor (d) HLA-C2 ligand (dC2) ligand increases CR concerning their presence (13.1% vs. 5.6%; = 0.018). A significant increase of CR was observed in rKIR2DL3/dC1 ( = 0.015), rKIR2DS4/dC1 ( = 0.014) and rKIR2DL3/rKIR2DS4/dC1 ( = 0.006). Long-term patient survival was significantly lower in rKIR2DS1rKIR2DS4/dC1 at 5-10 years post-transplant. This study shows the influence of rKIR/dHLA-C combinations and aKIR gene-gene mismatches in increasing CR and KIR2DS1/C1-ligands and the influence of KIR2DS4/C1-ligands in long-term graft survival.

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