Publication: KIR gene mismatching and KIR/C ligands in liver transplantation: consequences for short-term liver allograft injury
Authors
López Álvarez, María R. ; Campillo, José A. ; Moya Quiles, María Rosa ; Bolarín, José Miguel ; Peña, Jesús de la ; Salgado, Gema ; García Alonso, Ana M. ; Muro, Manuel ; Miras, Manuel ; Alonso, Clara ; Álvarez López, María Rocio ; Minguela, Alfredo ; Gimeno Arias, Lourdes ; Legaz Pérez, Isabel
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Publisher
Lippincott, Williams & Wilkins
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DOI
https://doi.org/10.1097/TP.0b013e318286486c
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info:eu-repo/semantics/article
Description
© 2013 Lippincott Williams & Wilkins. This document is the Published version of a Published Work that appeared in final form in Transplantation. To access the final edited and published work see https://doi.org/10.1097/TP.0b013e318286486c
Abstract
Background. Killer immunoglobulin-like receptors (KIRs) bind human leukocyte antigen (HLA) class-I (HLA-I) ligands and regulate functions of natural killer cells and subsets of T cells. KIR/HLA-I interactions allow predicting natural killer cell alloreactivity in hematopoietic stem cell transplantation and in HLA-compatible kidney transplants, but its meaning in liver transplantation remains controversial. Methods. KIR and HLA genotypes were studied in 402 liver transplants, using sequence-specific oligonucleotides and primer methods. Recipients and donor KIRs, HLA-C genotypes, KIR gene mismatches (MMs) between recipient-donor pairs, and KIR/HLA-ligand combinations were analyzed in overall transplantations, in the acute rejection (AR; n=110) and non-AR (n=292) groups. Results.
KIR gene MMs between recipients and donors, mainly in activating KIRs, and KIR2DL3 and KIR2DS1 of recipients in the presence of donor C2 ligands, significantly enhanced early AR rate (P<0.05), with KIR2DL3+ and KIR2DS1+ exhibiting a synergic effect in dependence of the donor C2 ligand number (χ2=7.662, P=0.022). KIR2DL3, KIR2DS1, and also KIR2DS4+ significantly influenced short-term graft survival, with a benefit for transplantations combining KIR2DL3+ recipients and donors having C1 ligands (log rank, P<0.019 at 1 year; hazards ratio [HR], 0.321; 95% confidence interval [CI], 0.107–0.962; P=0.042), whereas KIR2DS1+ and KIR2DS4+ recipients combined with donors lacking C1 ligands (C2/C2) exhibited a worse graft survival (log rank, P=0.035 at 6 months; HR, 7.713; 95% CI, 2.156–27.369; P=0.002 for KIR2DS1+; and log rank, P=0.006 at 1 year; HR, 3.794; 95% CI, 1.267–11.365; P=0.017 for KIR2DS4). Conclusions. This study shows that KIR gene-gene MMs increase AR and that KIRs/C ligands associated to AR and KIR2DS4+/C ligands also influence short-term graft survival.
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Citation
Transplantation Journal 2013 95(8): 1037-1044
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