Transplantation

Skip Navigation LinksHome > April 27, 2013 - Volume 95 - Issue 8 > KIR Gene Mismatching and KIR/C Ligands in Liver Transplantat...
Transplantation:
doi: 10.1097/TP.0b013e318286486c
Clinical and Translational Research

KIR Gene Mismatching and KIR/C Ligands in Liver Transplantation: Consequences for Short-Term Liver Allograft Injury

Legaz, Isabel1; López-Álvarez, María R.1; Campillo, José A.1; Moya-Quiles, María R.1; Bolarín, José M.1; de la Peña, Jesus2; Salgado, Gema1; Gimeno, Lourdes1; García-Alonso, Ana M.1; Muro, Manuel1; Miras, Manuel1,3; Alonso, Clara4; Álvarez-López, María R.1; Minguela, Alfredo1,5

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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.

© 2013 Lippincott Williams & Wilkins, Inc.

 



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