罗马尼亚慢性丙型肝炎患者的 HLA 等位基因和 KIR 基因。

HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C.

机构信息

Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. .

Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. .

出版信息

J Gastrointestin Liver Dis. 2020 Oct 27;29(4):595-601. doi: 10.15403/jgld-2546.

DOI:10.15403/jgld-2546

PMID:33118540

Abstract

BACKGROUND AND AIMS

The role of natural killer (NK) cells in the defense against hepatitis C virus (HCV) infection involve both innate and adaptive immunity. NK cells express a large panel of inhibitory and activating receptors who bind human leukocyte antigen (HLA) class I receptors. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic of these receptors being encoded by genes distributed differently in unrelated individuals. The aim of this study was to look at the immune response in chronic HCV patients by assessing NK-KIR genes and their corresponding HLA ligands.

METHODS

We genotyped 127 chronically HCV-infected patients and 130 non-infected healthy individuals for both KIR genes and their HLA ligands. The HLA-A, HLA-B, HLA-C genotypes were analyzed using polymerase chain reaction high-resolution typing.

RESULTS

KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3, KIR2DP1, KIR3DP1 genes were significantly increased in the HCV group compared to healthy individual. Analysis of various HLA haplotypes revealed different HLA alleles associated with increased susceptibility to HCV infection. Thus, HLA A23:01 was more frequent in the patients' group than in the controls (p=0.030). At the same time HLA B44:02 and C*04:02 were significantly elevated in HCV-positive patients (p=0.008 and respectively p= 0.007).

CONCLUSIONS

These results suggest that the expression of KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3 genes and the association with HLA alleles such as HLA A23:01, B44:02, C*04:02 may increase the patient susceptibility to chronic HCV infection.

摘要

背景与目的

自然杀伤（NK）细胞在防御丙型肝炎病毒（HCV）感染中的作用涉及先天免疫和适应性免疫。NK 细胞表达一系列抑制性和激活性受体，这些受体与人类白细胞抗原（HLA）I 类受体结合。杀伤细胞免疫球蛋白样受体（KIR）是这些受体中最具多态性的受体，由分布在不同个体中的不同基因编码。本研究旨在通过评估 NK-KIR 基因及其相应的 HLA 配体来研究慢性 HCV 患者的免疫反应。

方法

我们对 127 例慢性 HCV 感染患者和 130 例非感染健康个体进行了 KIR 基因及其 HLA 配体的基因分型。采用聚合酶链反应高分辨率分型法分析 HLA-A、HLA-B、HLA-C 基因型。

结果

与健康个体相比，HCV 组的 KIR2DL3、KIR2DL5、KIR2DS4norm、KIR3DL3、KIR2DP1、KIR3DP1 基因显著增加。对各种 HLA 单倍型的分析显示，不同的 HLA 等位基因与 HCV 感染的易感性增加有关。因此，HLA A23:01 在患者组中的频率高于对照组（p=0.030）。同时，HLA B44:02 和 C*04:02 在 HCV 阳性患者中显著升高（p=0.008 和分别 p=0.007）。