Ⅰ型自身免疫性肝炎患者IL28RA、PD-L1表达及与肝功能的相关性分析

Expressions of IL28RA and PD-L1 and their correlations with liver function in patients with type 1 autoimmune hepatitis

摘要:

目的 分析Ⅰ型自身免疫性肝炎（AIH）患者白细胞介素-28受体拮抗剂（IL28RA）、程序性细胞死亡因子配体1（PD-L1）表达及与肝功能的关系。方法 选取2018年2月—2023年3月仙桃市第一人民医院收治的Ⅰ型AIH患者85例，其中活动期53例（重度炎症组8例、中度炎症组12例和轻度炎症组33例）、缓解期32例。在超声引导下通过BARD一次性全自动活检枪实施肝穿刺活检术取得肝组织，另取同期该院收治的27例肝血管瘤患者（经手术取得肝组织）为对照组。采用ABC法测定肝组织PD-L1蛋白含量，荧光实时荧光定量聚合酶链反应检测肝组织IL28RA基因表达，比较肝功能指标［γ-谷氨酰转肽酶（γ-GT）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）］水平及肝组织IL28RA、PD-L1表达，分析肝组织IL28RA、PD-L1表达与肝功能指标的相关性。结果 活动期患者IL28RA相对表达量低于缓解期患者（P <0.05），PD-L1高于缓解期患者（P <0.05）。活动期患者TBIL、AST、γ-GT、ALT水平均高于缓解期患者（P <0.05）。AIH组IL28RA基因相对表达量低于对照组（P <0.05），PD-L1蛋白含量高于对照组（P <0.05）。与缓解期患者相比，各炎症组IL28RA基因相对表达量降低（P <0.05），PD-L1、AST、ALT、TBIL、γ-GT、IgG水平均升高（P <0.05）。Ⅰ型AIH患者IL28RA表达与AST、ALT、TBIL均呈负相关（r =-0.567、-0.671和-0.549，均P =0.000）；PD-L1表达与AST、ALT、TBIL、血清IgG均呈正相关（r =0.643、0.598、0.552和0.476，均P =0.000）。结论 Ⅰ型AIH患者与IL28RA、PD-L1表达及与肝功能密切相关。Ⅰ型AIH患者IL28RA表达下调，PD-L1表达上调。IL28RA表达与肝功能、肝组织炎症活动度呈负相关，PD-L1表达与肝功能、肝组织炎症活动度及血清IgG水平呈正相关。

Abstract:

Objective To analyze the expressions of interleukin 28 receptor α (IL28RA) and programmed cell death ligand 1 (PD-L1) and their correlations with the liver function in patients with type 1 autoimmune hepatitis (AIH).Methods The 85 patients with type 1 AIH admitted to our hospital between February 2018 and March 2023 were selected, including 53 patients in the active phase (8 with severe inflammation, 12 with moderate inflammation, and 33 with mild inflammation) and 32 patients in the remission phase. Liver tissue samples were obtained by ultrasound-guided percutaneous liver biopsy using the BARD disposable automatic biopsy gun. Another 27 patients with hepatic hemangioma treated in our hospital during the same period (liver tissue samples obtained by surgery) were selected as the control group. The expression level of PD-L1 in liver tissues was determined by the ABC method, and the expression level of IL28RA in liver tissues was detected by quantitative real-time polymerase chain reaction. The levels of indicators for liver function [γ-glutamyltransferase (γ-GT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) ] and expressions of IL28RA and PD-L1 in liver tissues were compared, and the correlations between the expressions of IL28RA and PD-L1 in liver tissues and the indicators for liver function were analyzed.Results The relative expression of IL28RA in patients in the active phase was lower than that in patients in the remission phase (P < 0.05), and the relative expression of PD-L1 in patients in the active phase was higher than that in patients in the remission phase (P < 0.05). The levels of TBIL, AST, γ-GT and ALT in patients in the active phase were all higher than those in patients in the remission phase (P < 0.05). The relative expression of IL28RA in the AIH group was lower than that in the control group (P < 0.05), and the relative expression of PD-L1 in the AIH group was higher than that in the control group (P < 0.05). Compared with patients in the remission phase, the relative expressions of IL28RA were lower (P < 0.05), and the levels of PD-L1, AST, ALT, TBIL, γ-GT and IgG were higher in patients with severe, moderate and mild inflammation (P < 0.05). The expression of IL28RA was negatively correlated with the levels of AST, ALT, and TBIL in patients with type I AIH (r = -0.567, -0.671, and -0.549, all P = 0.000). The expression of PD-L1 was positively correlated with the levels of AST, ALT, TBIL and IgG in patients with type I AIH (r = 0.643, 0.598, and 0.052, all P = 0.000).Conclusion In patients with type I AIH, the expressions of IL28RA and PD-L1 are closely associated with the liver function. The expression of IL28RA is down-regulated and the expression of PD-L1 is up-regulated in these patients. The expression of IL28RA is negatively correlated with the liver function and the degree of inflammation in liver tissues, while the expression of PD-L1 is positively correlated with the liver function, the degree of inflammation in liver tissues and the serum level of IgG.