Denk Gerald, Omary Ahmed-Jawid, Reiter Florian Paul, Hohenester Simon, Wimmer Ralf, Holdenrieder Stefan, Rust Christian
Department of Medicine II - Grosshadern, University of Munich, Munich, Germany.
Hepatol Res. 2014 Dec;44(13):1286-98. doi: 10.1111/hepr.12304. Epub 2014 Feb 28.
Hepatic apoptosis is involved in the pathogenesis of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The aim of our study was to quantify distinct markers of apoptosis in sera of patients with AIH, PBC and PSC, and to evaluate correlation with markers of disease activity and prognosis.
Sera of patients with AIH, PBC and PSC, and of healthy controls were collected and distinct cell death markers were quantified using a bead-based multiplex enzyme linked immunosorbent assay (soluble intracellular adhesion molecule [sICAM], macrophage migration inhibitory factor [MIF], soluble Fas [sFas], plasminogen activator inhibitor 1 [PAI-1]) or single enzyme-linked immunosorbent assays (DNAse, M30, M65).
In comparison with healthy controls, the apoptotic markers sFas, sICAM (only in PSC patients), M30 and the cell death marker M65 were substantially elevated in sera of patients with immune-mediated liver diseases, whereas DNAse activity was reduced. Interestingly, patients with advanced PSC presented with higher levels of sICAM, M30 and M65 than patients with mild PSC. Regression analysis revealed correlations between serum levels of sICAM, M30 and M65 with the Mayo Risk Score for PSC, and of M65 with the Mayo Risk Score for PBC.
Concentrations of the serum markers of apoptosis sFas and M30 and of the marker of total cell death M65 are elevated in patients with immune-mediated liver diseases, whereas activity of DNAse is reduced. In patients with PSC, sICAM, M30 and M65 may serve as indicators for disease activity and prognosis.
肝凋亡参与自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）等免疫介导性肝病的发病机制。我们研究的目的是对AIH、PBC和PSC患者血清中不同的凋亡标志物进行定量，并评估其与疾病活动和预后标志物的相关性。
收集AIH、PBC和PSC患者以及健康对照者的血清，使用基于微珠的多重酶联免疫吸附测定法（可溶性细胞间黏附分子[sICAM]、巨噬细胞迁移抑制因子[MIF]、可溶性Fas[sFas]、纤溶酶原激活物抑制剂1[PAI-1]）或单酶联免疫吸附测定法（脱氧核糖核酸酶、M30、M65）对不同的细胞死亡标志物进行定量。
与健康对照相比，免疫介导性肝病患者血清中的凋亡标志物sFas、sICAM（仅PSC患者）、M30和细胞死亡标志物M65显著升高，而脱氧核糖核酸酶活性降低。有趣的是，晚期PSC患者的sICAM、M30和M65水平高于轻度PSC患者。回归分析显示，sICAM、M30和M65的血清水平与PSC的梅奥风险评分相关，M65与PBC的梅奥风险评分相关。
免疫介导性肝病患者血清中凋亡标志物sFas和M30以及总细胞死亡标志物M65的浓度升高，而脱氧核糖核酸酶活性降低。在PSC患者中，sICAM、M30和M65可作为疾病活动和预后的指标。
