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KIR/HLA 配体免疫遗传学标志物与保加利亚人群乙型肝炎病毒感染结局的关系。

KIR/HLA ligands immunogenetics markers associated with outcome of hepatitis B virus infection in the Bulgarian population.

机构信息

Clinic of Hematology, Military Medical Academy, MHAT, Sofia, Bulgaria.

Clinic of Infection Diseases, Military Medical Academy, MHAT, Sofia, Bulgaria.

出版信息

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2021 Sep;165(3):270-276. doi: 10.5507/bp.2020.043. Epub 2020 Sep 21.

Abstract

BACKGROUND

Hepatitis B virus (HBV) infection is one of the most common infections worldwide, having negative impact on world health due to the tendency for chronification with late complications such as liver cirrhosis and hepatocellular carcinoma. Natural killer (NK) cells as part of innate antiviral defense influence the clinical course of HBV infection: elimination of the virus or chronic disease.

AIM

Therefore, we investigated the polymorphisms of the main gene systems, regulating NK-cell function: killer cell immunoglobulin-like receptors (KIRs) and their appropriate HLA class I ligands in 144 HBV infected patients (124 chronic carriers and 20 spontaneously recoved) and 126 ethnically matched healthy controls from the Bulgarian population in a case-control study.

METHODS

KIRs and HLA ligands were determined by PCR-SSP or PCR high-resolution typing methods.

RESULTS

KIR2DL5B allele variant was significantly less frequent in spontaneously recovered (SR) patients compared to healthy controls (10.0% vs. 45.5%, P=0.006). The presence of KIR3DL1*004 allele was higher in chronic HBV carriers (CH) than in controls (33.1% vs. 17.6%, P=0.036). Additionally, SR patients differed from healthy individuals by the lower frequency of HLA-Bw4 group ligands (30.0% vs 63.7%, P=0.015). Three KIR genotypes were found more frequent in healthy in comparison with HBV infected individuals: ID2 (13.5% vs 5.6%, P=0.025), KIR genotype containing 6 activating KIRs (18.0% vs 7.6%, P=0.017), and KIR genotype composed of 4 activating and 5 inhibitory KIRs (23.8% vs 5.6%, P=0.001).

CONCLUSION

These data suggest that inherited KIR and HLA class I ligand polymorphisms may influence the clinical course of HBV infection.

摘要

背景

乙型肝炎病毒(HBV)感染是全球最常见的感染之一,由于其慢性化并伴有晚期并发症(如肝硬化和肝细胞癌),对世界健康产生了负面影响。自然杀伤(NK)细胞作为先天抗病毒防御的一部分,影响 HBV 感染的临床过程:清除病毒或慢性疾病。

目的

因此,我们在病例对照研究中调查了调节 NK 细胞功能的主要基因系统,即杀伤细胞免疫球蛋白样受体(KIR)及其适当的 HLA Ⅰ类配体的多态性,在 144 例 HBV 感染患者(124 例慢性携带者和 20 例自发恢复者)和 126 名来自保加利亚人群的种族匹配健康对照中进行了研究。

方法

通过 PCR-SSP 或 PCR 高分辨率分型方法确定 KIR 和 HLA 配体。

结果

与健康对照组相比,自发恢复(SR)患者中 KIR2DL5B 等位基因变异体明显较少(10.0%比 45.5%,P=0.006)。慢性 HBV 携带者(CH)中 KIR3DL1*004 等位基因的存在高于对照组(33.1%比 17.6%,P=0.036)。此外,SR 患者与健康个体相比,HLA-Bw4 组配体的频率较低(30.0%比 63.7%,P=0.015)。与 HBV 感染个体相比,三种 KIR 基因型在健康个体中更为常见:ID2(13.5%比 5.6%,P=0.025)、包含 6 种激活 KIR 的 KIR 基因型(18.0%比 7.6%,P=0.017)和由 4 种激活 KIR 和 5 种抑制 KIR 组成的 KIR 基因型(23.8%比 5.6%,P=0.001)。

结论

这些数据表明,遗传的 KIR 和 HLA Ⅰ类配体多态性可能影响 HBV 感染的临床过程。

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