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[组织蛋白酶S在原发性胆汁性胆管炎中的作用]

[The effect of Cathepsin S in primary biliary cholangitis].

作者信息

Luo X, Li X, Du Z R, Peng Y, Deng C W, Fei Y Y

机构信息

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Key Laboratory of Rheumatology and Cinical Immunology, Ministry of Education, Beijing 100730, China.

Department of Rheumatology and Immunology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2019 Feb 19;99(7):505-509. doi: 10.3760/cma.j.issn.0376-2491.2019.07.006.

DOI:10.3760/cma.j.issn.0376-2491.2019.07.006
PMID:30786347
Abstract

To explore the effect of cathepsin (Cat) S in primary biliary cholangitis (PBC). The serum of PBC patients and Hepatitis B virus (HBV) patients were collected in Peking Union Medical College Hospital from August 2016 to July 2017 and the liver tissue of PBC were collected from March 2010 to July 2013. Indirect enzyme-linked immunosorbent assay (ELISA) was used to detect the serum concentrations of total-and pro-Cat S respectively in 24 PBC patients, 24 Hepatitis B patients and 24 healthy controls. The relation between the serum levels of Cat S and cholestasis biochemical indexes and the serum levels of immunoglobulin (Ig) M, G were analyzed. Immunofluorescence analysis of liver tissue was performed to detect macrophage infiltration and Cat S expression. The data was analyzed by student's -test, spearman correlation analysis, and receiver operating characteristic (ROC) curve was used to obtain an optimal cutoff value. The serum levels of total-Cat S, pro-Cat S and active-Cat S in PBC group were significantly higher than those in healthy controls and HBV controls (0.05). There was a correlation between serum total-Cat S and ALP and GGT in patients with PBC (0.05). There was a moderate correlation between pro-Cat S and ALP and GGT (0.05) and total Cat S was associated with IgG (0.05). The area under ROC curve (AUC) of total-Cat S, pro-Cat S and active-Cat S was 0.85(0.01), 0.65(0.05) and 0.77(0.01), respectively. The optimal cut-off value was 11.30、7.81 and 5.93 pg/L, respectively, with the sensitivity of 0.81, 0.53 and 0.53 and specificity of 0.82, 0.81 and 0.96. Liver tissue immunofluorescence revealed macrophage infiltration in the liver of PBC patients. The average percentage of macrophages and Cat S co-expressed cells in mononuclear cells was 23.77%. The expression of Cat S in serum of patients with PBC is significantly higher than that of healthy controls and HBV patients, and is related to IgG and serum ALP, r-GT levels. Liver tissue macrophages were co-expressed with Cat S. Cat S may participate in the process of antigen presentation in the pathogenesis of PBC.

摘要

探讨组织蛋白酶(Cat)S在原发性胆汁性胆管炎(PBC)中的作用。于2016年8月至2017年7月在北京协和医院收集PBC患者及乙型肝炎病毒(HBV)患者的血清,并于2010年3月至2013年7月收集PBC患者的肝组织。采用间接酶联免疫吸附测定(ELISA)分别检测24例PBC患者、24例乙型肝炎患者和24例健康对照者血清中总Cat S和前体Cat S的浓度。分析Cat S血清水平与胆汁淤积生化指标以及免疫球蛋白(Ig)M、G血清水平之间的关系。对肝组织进行免疫荧光分析以检测巨噬细胞浸润及Cat S表达。数据采用学生t检验、Spearman相关性分析,并使用受试者工作特征(ROC)曲线获得最佳临界值。PBC组血清总Cat S、前体Cat S和活性Cat S水平显著高于健康对照和HBV对照(P<0.05)。PBC患者血清总Cat S与碱性磷酸酶(ALP)和γ-谷氨酰转肽酶(GGT)之间存在相关性(P<0.05)。前体Cat S与ALP和GGT之间存在中度相关性(P<0.05),总Cat S与IgG相关(P<0.05)。总Cat S、前体Cat S和活性Cat S的ROC曲线下面积(AUC)分别为0.85(P<0.01)、0.65(P<0.05)和0.77(P<0.01)。最佳临界值分别为11.30、7.81和5.93 pg/L,敏感性分别为0.81、0.53和0.53,特异性分别为0.82、0.81和0.96。肝组织免疫荧光显示PBC患者肝脏中有巨噬细胞浸润。单核细胞中巨噬细胞与Cat S共表达细胞的平均百分比为23.77%。PBC患者血清中Cat S的表达明显高于健康对照和HBV患者,且与IgG及血清ALP、γ-GT水平相关。肝组织巨噬细胞与Cat S共表达。Cat S可能参与PBC发病机制中的抗原呈递过程。

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