KIR Gene Mismatching and KIR/C Ligands in Liver Transplantation

• DOI: 10.1097/tp.0b013e318286486c
• Publication Date: 2013-05-23T19:44:03Z
• Authors: Isabel Legaz; María R. López-Ál...; José A. Campillo; María R. Moya-Quiles; José M. Bolarín; Jesus de la Peña; Gema Salgado; Lourdes Gimeno; Ana M. García-Alonso; Manuel Muro; Manuel Miras; Clara Alonso; María R. Álvarez-...; Alfredo Minguela
• Keywords: Graft Rejection; Male; Time Factors; HLA-C Antigens; Ligands; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Receptors, KIR; Recurrence; T-Lymphocyte Subsets; Humans; Liver transplantation; Histocompatibility Testing; Graft Survival; Short-term graft survival; Middle Aged; Hepatitis C; KIR; Liver Transplantation; 3. Good health; Killer Cells, Natural; Receptors, KIR2DL3; HLA ligands; Acute rejection; Female

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.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.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).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.