Intrahepatic Expression of Programmed Death-1 and its Ligands in Patients with HBV-Related Acute-on-Chronic Liver Failure
Intrahepatic Expression of Programmed Death-1 and its Ligands in Patients with HBV-Related Acute-on-Chronic Liver Failure
复制标题
程序性死亡-1 及其配体在 HBV 相关慢性急性肝衰竭患者的肝内表达。
DOI：
10.1007/s10753-012-9525-7
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发表时间：
2013-02-01
期刊：
影响因子：
5.1
通讯作者：
Chen, Yongwen
中科院分区：
文献类型：
--
作者：
Cao, Dayan;Xu, Huan;Chen, Yongwen
B型肝炎病毒（HBV）感染是一个重大的公共卫生问题，由于对HBV相关的慢性加急性肝衰竭（HBV-ACLF）的发病机制缺乏了解以及缺乏有效的治疗方法，其预后极差。来自抑制性受体程序性死亡-1（PD-1）的信号已被证明参与调节感染性疾病的发病机制。然而，PD-1及其配体在HBV-ACLF患者中的表达还有待评估。本研究采用免疫组织化学方法检测了PD-1及其配体PD-L1和PD-L2在HBV-ACLF和慢性B型肝炎（CH B）患者肝活检组织中的表达。结果显示，所有三种分子在HBV-ACLF样本中观察到，并且它们的水平显著高于CHB。免疫荧光双标显示PD-1主要表达于CD 3（+）、CD 8（+）T细胞、CD 56（+）NK细胞、CD 68（+）巨噬细胞、CK-18（+）上皮细胞和CD 16（+）单核细胞。PD-L2主要表达于CK-18（+）上皮细胞和CD 31（+）内皮细胞。有趣的是，在HBV-ACLF的肝切片中观察到高水平的病毒诱导的促凝血分子纤维蛋白原样蛋白2（FGL 2），在这些患者的FGL 2（+）细胞上也观察到PD-L1和PD-L2表达。我们的综合结果表明，PD-L1和PD-L2的表达可能是识别和诊断ACLF的生物标志物，并且对其功能作用的明确理解将进一步阐明这种疾病的发病机制。
Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (HBV-ACLF) has an extremely poor prognosis due to a lack of understanding of pathogenesis as well as a lack of effective treatments. Signals from the inhibitory receptor programmed death-1 (PD-1) have been demonstrated to be involved in regulating the pathogenesis of infectious diseases. However, the expression of PD-1 and its ligands in HBV-ACLF patients has yet to be evaluated. In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in liver biopsies from HBV-ACLF as well as chronic hepatitis B (CHB) patients were analyzed by immunohistochemistry. The results showed that all three molecules were observed in the HBV-ACLF samples and their levels were significantly higher than they were in CHB. Immunofluorescence double-staining showed that PD-1 was found on CD3(+), CD8(+) T cells, CD56(+) NK cells, CD68(+) macrophages, CK-18(+) epithelial cells, and CD16(+) monocytes. The PD-L1 expression was observed on all cell types detected and the PD-L2 was chiefly on CK-18(+) epithelial cells and CD31(+) endothelial cells. Interestingly, high levels of virus-induced procoagulant molecule fibrinogen-like protein 2 (FGL2) were observed in liver sections from HBV-ACLF, and PD-L1 and PD-L2 expression was also observed on FGL2(+) cells in these patients. Our combined results suggest that the expression of PD-L1 and PD-L2 may be biomarkers to identify and diagnose ACLF, and a clear understanding of their functional roles should further elucidate the pathogenesis of this disease.