Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis
Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis
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原发性胆汁性肝硬化患者血浆 IL-35 水平较低
DOI：
10.1620/tjem.244.123
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发表时间：
2018-02-01
影响因子：
2.2
通讯作者：
Deng, Anmei
中科院分区：
文献类型：
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作者：
Li, Tengda;Huang, Yuanlan;Deng, Anmei
原发性胆汁性肝硬化（PBC）是一种自身免疫性肝病。其组织学特征，如进行性肝内胆管破坏、胆汁淤积和肝硬化，是由机体自身免疫性疾病引起的。白细胞介素（IL）-35具有两个亚基（p35和Ebi 3），并且是异二聚体细胞因子的IL-12家族的成员。IL-35具有免疫抑制功能，在许多自身免疫性疾病中发挥重要作用。在这项研究中，我们比较了70例PBC患者和70名健康人的血浆IL-35水平和外周血单个核细胞（PBMCs）中p35和Ebi 3的相对mRNA表达水平。结果显示，PBC患者PBMCs中Ebi 3 mRNA的相对表达水平低于健康人PBMCs，而p35 mRNA的相对表达水平与健康人PBMCs相似。PBC患者血浆IL-35浓度低于健康人。晚期PBC患者的血浆水平高于早期患者。在转化生长因子β（TGF-β）中也发现了不同阶段的可变血浆水平，TGF-β主要由调节性T细胞（TCFs）产生。IL-35与TGF-β水平呈正相关，IL-35在PBC患者的早期和晚期均能促进TGF-β的抑制功能。PBC患者血浆IL-35水平较低时，其典型临床参数如碱性磷酸酶或促炎细胞因子如干扰素-γ（IFN-γ）水平较高（各P < 0.05）。提示IL-35可能参与PBC的发病机制，并可能成为PBC诊断的潜在生物标志物。
Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-beta), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-beta levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-gamma), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.