Legaz Isabel, Bolarín Jose Miguel, Navarro Elena, Campillo Jose Antonio, Moya Rosa, Pérez-Cárceles María Dolores, Luna Aurelio, Osuna Eduardo, Miras Manuel, Muro Manuel, Minguela Alfredo, Alvarez López Rocio
Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence "Campus Mare Nostrum", Faculty of Medicine, University of Murcia, Murcia, Spain.
Research Institute on Ageing, University of Murcia, Murcia, Spain.
Arch Med Sci. 2019 Apr 9;17(3):764-774. doi: 10.5114/aoms.2019.84410. eCollection 2021.
The molecular mechanisms underlying alcoholic liver fibrosis and cirrhosis are not completely understood. Hepatic fibrosis involves the interplay of diverse cells and factors, including hepatic stellate cells (HSCs), Kupffer, NK cells, and T-lymphocyte subsets. Killer-cell immunoglobulin-like receptors (KIR) are membrane receptors involved in mediation between NK and activated HSCs, regulating NK cell function through their interaction with HLA-I molecules. The aim of this study was to analyse the genetic association between KIR genes and the susceptibility to or protection from alcoholic cirrhosis (AC) in a cohort of male AC patients undergoing liver transplantation (LT) with and without concomitant viral infections.
KIR genotyping was performed in nuclear DNA extracted from 281 AC patients and compared with 319 male controls.
Significant differences between total AC patients and healthy controls were only found in the case of KIR2DL2 and KIR2DS5. KIR2DL2 was significantly underrepresented in non-viral AC patients (52.6% vs. 63.3%; = 0.015), while patients heterozygous for KIR2DL2 were also underrepresented in the non-viral AC group compared with controls ( = 0.034). KIR2DS5 was overrepresented in this group compared with healthy controls ( = 0.002). All these observations were only evident in AC patients older than 54 years old.
Our data suggest a contrary effect of KIR2DL2 and KIR2DS5 in AC patients older than 54 years, in whom the presence of KIR2DL2 appears to be protective against AC, whereas the presence of KIR2DS5 seems to promote the fibrotic process, particularly in patients with no associated viral infection.
酒精性肝纤维化和肝硬化的分子机制尚未完全明确。肝纤维化涉及多种细胞和因子的相互作用，包括肝星状细胞（HSC）、库普弗细胞、自然杀伤（NK）细胞和T淋巴细胞亚群。杀伤细胞免疫球蛋白样受体（KIR）是参与NK细胞与活化HSC之间介导作用的膜受体，通过与HLA - I分子相互作用调节NK细胞功能。本研究旨在分析KIR基因与接受肝移植（LT）的男性酒精性肝硬化（AC）患者（伴或不伴病毒感染）对AC的易感性或保护性之间的遗传关联。
对从281例AC患者提取的核DNA进行KIR基因分型，并与319例男性对照进行比较。
仅在KIR2DL2和KIR2DS5方面发现AC患者与健康对照之间存在显著差异。KIR2DL2在非病毒感染的AC患者中显著减少（52.6%对63.3%；P = 0.015），而与对照相比，KIR2DL2杂合子患者在非病毒感染的AC组中也减少（P = 0.034）。与健康对照相比，该组中KIR2DS5增加（P = 0.002）。所有这些观察结果仅在年龄大于54岁的AC患者中明显。
我们的数据表明，KIR2DL2和KIR2DS5对年龄大于54岁的AC患者有相反作用，其中KIR2DL2的存在似乎对AC有保护作用，而KIR2DS5的存在似乎促进纤维化过程，特别是在无相关病毒感染的患者中。
