循环适应性免疫细胞在终末期肝病中的功能障碍

Livers Pub Date : 2023-08-04 DOI:10.3390/livers3030028
Tong Liu, Yasmina Chouik, F. Lebossé, W. Khamri
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引用次数: 0

摘要

终末期肝病(ESLD)从急性肝衰竭到代偿性晚期慢性肝病和不同阶段的失代偿性肝硬化(慢性失代偿、急性失代偿伴或不伴急性-慢性肝衰竭),疾病严重程度高,患者预后差。感染是ESLD患者的常见并发症,并与高死亡率相关。这种明显的感染易感性涉及多种机制,尤其是被称为免疫麻痹的免疫反应不足,这是肝硬化相关免疫功能障碍(CAID)的一部分。特别是在适应性免疫臂中,淋巴细胞损伤——包括激活不足、分泌效应分子的能力降低和免疫抑制表型增强——会导致系统免疫反应受损和感染风险增加。这篇综述总结了目前对ESLD中适应性免疫反应性改变及其潜在机制的认识。了解这些机制对于识别潜在的治疗靶点和应用抗微生物药物以外的靶向治疗(如免疫疗法)至关重要。
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Dysfunctions of Circulating Adaptive Immune Cells in End-Stage Liver Disease
End-stage liver disease (ESLD) from acute liver failure to compensated advanced chronic liver disease and decompensated cirrhosis at different stages (chronic decompensation, acute decompensation with or without acute-on-chronic liver failure) has high disease severity and poor patient outcome. Infection is a common complication in patients with ESLD and it is associated with a high mortality rate. Multiple mechanisms are involved in this marked susceptibility to infections, noticeably the inadequate immune response known as immune paresis, as part of cirrhosis-associated immune dysfunction (CAID). Specifically in the adaptive immune arm, lymphocyte impairments—including inadequate activation, reduced ability to secrete effector molecules and enhanced immune suppressive phenotypes—result in compromised systemic immune responses and increased risk of infections. This review summarises current knowledge of alterations in adaptive immune responsiveness and their underlying mechanisms in ESLD. Understanding these mechanisms is of crucial importance in the identification of potential therapeutic targets and applications of targeted treatments beyond antimicrobials, such as immunotherapy.
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