Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response
Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response
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DOI：
10.5114/ceh.2019.87642
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发表时间：
2019-01-01
影响因子：
1.5
通讯作者：
Sira, Mostafa M.
中科院分区：
文献类型：
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作者：
Agina, Hala A.;Ehsan, Nermine A.;Sira, Mostafa M.
研究目的：自身免疫性肝炎（AIH）的组织学特征是伴有界面性肝炎的侵袭性炎症和显着的淋巴浆细胞浸润。程序性死亡-1 (PD-1) 在活化的淋巴细胞上表达。 PD-1 与其配体 PD-L1 的结合导致细胞凋亡和死亡。我们的目的是评估 AIH 儿童中 PD-1 和 PD-L1 的免疫组织化学表达及其与治疗结果的关系。 材料和方法：将 31 名 AIH 儿童治疗前的肝活检与作为对照组的 30 名慢性丙型肝炎病毒（HCV）感染儿童进行比较。 PD-1在淋巴细胞中进行评估，而PD-L1在淋巴细胞、肝细胞、胆管上皮细胞、窦内皮细胞和库普弗细胞中进行评估。所有 AIH 患者均接受标准治疗。 结果：AIH 患者的平均 PD-1 显着高于 HCV 患者（29.19 +/- 18.5% vs. 15.2 +/- 10.1%；p = 0.002），而淋巴细胞上的 PD-L1 没有统计学显着差异（p = 0.853）。 PD-1 和 PD-L1 均与肝纤维化或炎症活动无关（均 p > 0.05）。与 HCV 患者相比，AIH 患者的 PD-1/PD-L1 比率显着较高，与有反应者相比，无反应的 AIH 患者的 PD-1/PD-L1 比率显着较高（46.9 vs. 6.58）。 PD-1 表达在应答者和非应答者中具有可比性 (p = 0.813)，而 PD-L1 在应答者中显着上调 (4.17 +/- 3.15% vs. 0.63 +/- 1.3%；p = 0.046)。 AIH 和 HCV 组的肝细胞、胆管上皮细胞、窦内皮细胞和 Kupffer 细胞上的 PD-L1 表达相当。结论：反映免疫攻击性的 PD-1/PD-L1 比值在 AIH 中显着高于 HCV 患者，而无应答 AIH 患者则显着高于应答者。
Aim of the study: Autoimmune hepatitis (AIH) is characterized histologically by aggressive inflammation with interface hepatitis and prominent lymphoplasmacytic infiltration. Programmed death-1 (PD-1) is expressed on activated lymphocytes. Engagement of PD-1 by its ligand PD-L1 leads to cell apoptosis and death. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in children with AIH, and its relation to treatment outcome.Material and methods: Pre-treatment liver biopsies of 31 children with AIH were compared to 30 children with chronic hepatitis C virus (HCV) infection as a control group. PD-1 was evaluated in lymphocytes, while PD-L1 was evaluated in lymphocytes, hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells. All AIH patients received the standard treatment.Results: The mean PD-1 was significantly higher in AIH than HCV patients (29.19 +/- 18.5% vs. 15.2 +/- 10.1%; p = 0.002) while there was no statistically significant difference as regards PD-L1 on lymphocytes (p = 0.853). Neither PD-1 nor PD-L1 correlated with either liver fibrosis or the inflammatory activity (p > 0.05 for all). PD-1/PD-L1 ratio was significantly higher in AIH compared to HCV patients and in non-responder AIH patients compared to responders (46.9 vs. 6.58). PD-1 expression was comparable in both responders and non-responders (p = 0.813), while PD-L1 was significantly upregulated in responders (4.17 +/- 3.15% vs. 0.63 +/- 1.3%; p = 0.046). PD-L1 expression on hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells was comparable in AIH and HCV groups.Conclusions: PD-1/PD-L1 ratio, which reflects immune aggression, was significantly higher in AIH compared to HCV patients and in non-responder AIH patients compared to responders.