The Role of Macrophage Migration Inhibitory Factor in Autoimmune Liver Disease
The Role of Macrophage Migration Inhibitory Factor in Autoimmune Liver Disease
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DOI：
10.1002/hep.26664
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发表时间：
2014-02-01
期刊：
影响因子：
13.5
通讯作者：
Bucala, Richard
中科院分区：
文献类型：
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作者：
Assis, David N.;Leng, Lin;Bucala, Richard
评估了细胞因子巨噬细胞移动抑制因子（MIF）及其受体CD 74在自身免疫性肝炎（AIH）和原发性胆汁性肝硬化（PBC）中的作用。在500多例AIH、PBC和对照组患者的DNA样本中，分析了两种MIF启动子多态性，一种功能性-794 CATT（5-8）微卫星重复序列（rs 5844572）和一种功能性-173 G/C单核苷酸多态性（rs755622）。我们发现，与PBC相比，AIH中促炎和高表达的-794 CATT（7）等位基因的频率较高，而与AIH和健康对照相比，PBC中的频率较低。应用酶联免疫吸附法检测165例AIH、PBC患者及正常对照血清中MIF及可溶性MIF受体（CD 74）的表达。与健康对照组相比，AIH和PBC患者的循环血清和肝脏MIF表达升高。我们还鉴定了MIF受体的截短循环形式，CD 74，其从肝星状细胞释放并结合MIF，中和其信号转导活性。PBC患者的CD 74水平显著高于AIH和对照组。结论：这些数据表明，在MIF基因座AIH和PBC的不同的遗传和免疫病理基础。循环MIF和MIF受体谱将PBC与AIH的更多炎性表型区分开来，并且可能在这些疾病的发病机制中起作用并作为生物标志物。（肝病学2014;59：580-591）
The role of the cytokine, macrophage migration inhibitory factor (MIF), and its receptor, CD74, was assessed in autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Two MIF promoter polymorphisms, a functional -794 CATT(5-8) microsatellite repeat (rs5844572) and a -173 G/C single-nucleotide polymorphism (rs755622), were analyzed in DNA samples from over 500 patients with AIH, PBC, and controls. We found a higher frequency of the proinflammatory and high-expression -794 CATT(7) allele in AIH, compared to PBC, whereas lower frequency was found in PBC, compared to both AIH and healthy controls. MIF and soluble MIF receptor (CD74) were measured by enzyme-linked immunosorbent assay in 165 serum samples of AIH, PBC, and controls. Circulating serum and hepatic MIF expression was elevated in patients with AIH and PBC versus healthy controls. We also identified a truncated circulating form of the MIF receptor, CD74, that is released from hepatic stellate cells and that binds MIF, neutralizing its signal transduction activity. Significantly higher levels of CD74 were found in patients with PBC versus AIH and controls. Conclusions: These data suggest a distinct genetic and immunopathogenic basis for AIH and PBC at the MIF locus. Circulating MIF and MIF receptor profiles distinguish PBC from the more inflammatory phenotype of AIH and may play a role in pathogenesis and as biomarkers of these diseases. (Hepatology 2014;59:580-591)