KIR 基因错配和肝移植中的 KIR/C 配体：对短期肝移植物损伤的影响。

KIR gene mismatching and KIR/C ligands in liver transplantation: consequences for short-term liver allograft injury.

机构信息

Immunology Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas and Instituto Murciano de Investigación Biomédica, Murcia, Spain.

出版信息

Transplantation. 2013 Apr 27;95(8):1037-44. doi: 10.1097/TP.0b013e318286486c.

DOI:10.1097/TP.0b013e318286486c

PMID:23478359

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.

摘要

背景

杀伤细胞免疫球蛋白样受体（KIR）与人类白细胞抗原（HLA）I 类（HLA-I）配体结合，调节自然杀伤细胞和 T 细胞亚群的功能。KIR/HLA-I 相互作用可预测造血干细胞移植和 HLA 匹配肾移植中的自然杀伤细胞同种异体反应，但在肝移植中的意义仍存在争议。

方法

使用序列特异性寡核苷酸和引物方法，在 402 例肝移植中研究了 KIR 和 HLA 基因型。在整体移植、急性排斥（AR；n=110）和非 AR（n=292）组中分析了受者和供者的 KIR、HLA-C 基因型、受者-供者对的 KIR 基因错配（MM）以及 KIR/HLA 配体组合。

结果

受者和供者之间的 KIR 基因 MM，主要是在激活的 KIR 中，以及存在供体 C2 配体时受者的 KIR2DL3 和 KIR2DS1，显著增加了早期 AR 率（P<0.05），KIR2DL3 和 KIR2DS1 存在协同作用，取决于供体 C2 配体的数量（χ2=7.662，P=0.022）。KIR2DL3、KIR2DS1 和 KIR2DS4 显著影响短期移植物存活率，KIR2DL3 受者和具有 C1 配体的供者联合移植具有获益（对数秩检验，1 年时 P<0.019；风险比[HR]，0.321；95%置信区间[CI]，0.107-0.962；P=0.042），而 KIR2DS1 和 KIR2DS4 受者与缺乏 C1 配体的供者（C2/C2）联合移植的移植物存活率较差（对数秩检验，6 个月时 P=0.035；HR，7.713；95%CI，2.156-27.369；P=0.002 用于 KIR2DS1；对数秩检验，1 年时 P=0.006；HR，3.794；95%CI，1.267-11.365；P=0.017 用于 KIR2DS4）。