Agina Hala A, Ehsan Nermine A, Abd-Elaziz Taghreed A, Abd-Elfatah Ghada A, Said Eman M, Sira Mostafa M
Pathology Department, Faculty of Medicine, Benha University, Egypt.
Pathology Department, National Liver Institute, Menoufia University, Egypt.
Clin Exp Hepatol. 2019 Sep;5(3):256-264. doi: 10.5114/ceh.2019.87642. Epub 2019 Sep 5.
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.
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.
The mean PD-1 was significantly higher in AIH than HCV patients (29.19 ±18.5% vs. 15.2 ±10.1%; = 0.002) while there was no statistically significant difference as regards PD-L1 on lymphocytes ( = 0.853). Neither PD-1 nor PD-L1 correlated with either liver fibrosis or the inflammatory activity ( > 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 ( = 0.813), while PD-L1 was significantly upregulated in responders (4.17 ±3.15% vs. 0.63 ±1.3%; = 0.046). PD-L1 expression on hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells was comparable in AIH and HCV groups.
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.
自身免疫性肝炎（AIH）在组织学上的特征为伴有界面性肝炎的侵袭性炎症和显著的淋巴浆细胞浸润。程序性死亡蛋白1（PD-1）在活化淋巴细胞上表达。PD-1与其配体PD-L1结合会导致细胞凋亡和死亡。我们旨在评估AIH患儿中PD-1和PD-L1的免疫组化表达及其与治疗结果的关系。
将31例AIH患儿的治疗前肝活检与30例慢性丙型肝炎病毒（HCV）感染患儿作为对照组进行比较。在淋巴细胞中评估PD-1，而在淋巴细胞、肝细胞、胆管上皮细胞、窦状内皮细胞和库普弗细胞中评估PD-L1。所有AIH患者均接受标准治疗。
AIH患者的平均PD-1显著高于HCV患者（29.19±18.5%对15.2±10.1%；P = 0.002），而淋巴细胞上的PD-L1无统计学显著差异（P = 0.853）。PD-1和PD-L1均与肝纤维化或炎症活动无关（所有P>0.05）。与HCV患者相比，AIH患者以及与反应者相比，无反应的AIH患者的PD-1/PD-L1比值显著更高（46.9对6.58）。反应者和无反应者的PD-1表达相当（P = 0.813），而反应者的PD-L1显著上调（4.17±3.15%对0.63±1.3%；P = 0.046）。AIH组和HCV组中肝细胞、胆管上皮细胞、窦状内皮细胞和库普弗细胞上的PD-L1表达相当。
反映免疫侵袭的PD-1/PD-L1比值在AIH患者中显著高于HCV患者，在无反应的AIH患者中显著高于反应者。
