Fan Yu-Chen, Zhang Yuan-Yuan, Wang Na, Sun Yan-Yan, Wang Kai
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
Institute of Hepatology, Shandong University, Jinan, China.
Oncotarget. 2017 May 9;8(19):30781-30792. doi: 10.18632/oncotarget.15683.
Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a newly negative immune regulator but its role in different immune phases of patients with chronic hepatitis B (CHB) is unknown. We determined the mRNA levels of TIPE2, interleukin-6, interleukin-10, tumor necrosis factors-α and interferon-γ in peripheral blood mononuclear cells from 205 naïve treated CHB patients and 15 healthy controls by quantitative real time polymerase chain reaction. Intrahepatic TIPE2 protein was also determined using immunohistochemistry staining. The TIPE2 mRNA level in CHB patients was significantly higher than that in healthy controls. Moreover, the TIPE2 mRNA level in immune clearance (IC) phases was significantly higher than that in immune tolerance (IT) phase; whereas TIPE2 mRNA in HBeAg negative hepatitis (ENH) was obviously higher than low replication (LR) phase. Furthermore, the optional cut off values of 2.02 and 1.59 for TIPE2 mRNA level have strong power in identifying IC and ENH from IT and LR. In addition, intrahepatic TIPE2 protein was predominantly located in hepatocyte plasma and correlated with hepatic inflammatory and fibrosis. Multivariate analysis showed tumor necrosis factors-α, interferon-γ and HBV DNA load were independently correlated with TIPE2 level. In conclusion, TIPE2 might be associated to the immune clearance of patients with chronic hepatitis B.
肿瘤坏死因子-α诱导蛋白8样2(TIPE2)是一种新发现的负性免疫调节因子,但其在慢性乙型肝炎(CHB)患者不同免疫阶段中的作用尚不清楚。我们通过定量实时聚合酶链反应测定了205例初治CHB患者和15例健康对照者外周血单个核细胞中TIPE2、白细胞介素-6、白细胞介素-10、肿瘤坏死因子-α和干扰素-γ的mRNA水平。还采用免疫组织化学染色法测定肝内TIPE2蛋白。CHB患者的TIPE2 mRNA水平显著高于健康对照者。此外,免疫清除(IC)期的TIPE2 mRNA水平显著高于免疫耐受(IT)期;而HBeAg阴性肝炎(ENH)中的TIPE2 mRNA明显高于低复制(LR)期。此外,TIPE2 mRNA水平的最佳截断值2.02和1.59在区分IC期和ENH期与IT期和LR期方面具有强大的鉴别能力。此外,肝内TIPE2蛋白主要定位于肝细胞浆,与肝脏炎症和纤维化相关。多因素分析显示,肿瘤坏死因子-α、干扰素-γ和HBV DNA载量与TIPE2水平独立相关。总之,TIPE2可能与慢性乙型肝炎患者的免疫清除有关。