Peng Bo, Huang Xueyong, Nakayasu Ernesto S, Petersen John R, Qiu Suimin, Almeida Igor C, Zhang Jian-Ying
Border Biomedical Research Center, Department of Biological Sciences, The University of Texas at El Paso , El Paso, Texas 79968, United States.
J Proteome Res. 2013 Apr 5;12(4):1789-96. doi: 10.1021/pr3011342. Epub 2013 Mar 15.
Liver fibrosis results from extracellular matrix accumulation during the wound healing process when the liver is insulted with chronic viral infection, inflammation, or alcoholic diseases. The current diagnosis of liver fibrosis is mainly dependent on biopsy, which is an invasive approach. Identification of serological biomarkers has been considered as the most promising way for early detection of the disease. Although several biomarkers in liver fibrosis have been identified, the problem is that these markers can be also detected in fibrogenesis that occurred in other organs. In this study, we have identified and characterized some cellular proteins that can be recognized by autoantibodies in the sera from patients with precirrhotic stage of liver fibrosis. Among 180 sera from patients with liver fibrosis, 14.4% (26/180) of sera contained autoantibody against a protein migrating around 47 kDa on SDS-PAGE gel. Indirect immunofluorescence assay using purified autoantibody against the 47-kDa protein showed that this protein mainly localized in the cytoplasm. Using immunoproteomic approach, the 47-kDa protein was identified as alpha-enolase. In further study, the frequency of antialpha-enolase antibody in sera from patients with precirrhotic stage of liver fibrosis (21.6%, 27/125) was significantly higher than that in sera from patients with cirrhosis (9.1%, 5/55) and liver cancer (14.3%, 12/84), as well as in sera from healthy individuals (4.1%, 3/74). Therefore, alpha-enolase is an autoantigen that elicits autoimmune response in liver fibrosis and can be a potential prognostic factor for liver fibrosis diagnosis.
肝纤维化是在肝脏受到慢性病毒感染、炎症或酒精性疾病侵害时,伤口愈合过程中细胞外基质积累的结果。目前肝纤维化的诊断主要依赖于活检,这是一种侵入性方法。血清生物标志物的鉴定被认为是早期检测该疾病最有前景的方法。尽管已经鉴定出了几种肝纤维化生物标志物,但问题在于这些标志物在其他器官发生的纤维化过程中也能被检测到。在本研究中,我们鉴定并表征了一些细胞蛋白,这些蛋白可被肝纤维化肝硬化前期患者血清中的自身抗体识别。在180份肝纤维化患者的血清中,14.4%(26/180)的血清含有针对在SDS-PAGE凝胶上迁移约47 kDa的一种蛋白的自身抗体。使用针对47 kDa蛋白的纯化自身抗体进行间接免疫荧光分析表明,该蛋白主要定位于细胞质中。采用免疫蛋白质组学方法,将47 kDa蛋白鉴定为α-烯醇化酶。在进一步研究中,肝纤维化肝硬化前期患者血清中抗α-烯醇化酶抗体的频率(21.6%,27/125)显著高于肝硬化患者血清(9.1%,5/55)、肝癌患者血清(14.3%,12/84)以及健康个体血清(4.1%,3/74)。因此,α-烯醇化酶是一种在肝纤维化中引发自身免疫反应的自身抗原,并且可能是肝纤维化诊断的一个潜在预后因素。