Clinical significance of antinuclear antibodies in primary liver cancer and molecular characterization of thier target antigens

DNA拓扑异构酶II是新发现的与原发性肝癌患者抗核抗体反应的自身抗原之一。另一种新的自身抗原是肝癌ANA的靶标，一种120千道尔顿的核仁蛋白，已经被表征。这被证明是定位在核仁的密集纤维区。目前正在利用分子克隆技术研究该蛋白的分子性质。在587例慢性肝病患者的前瞻性研究中，6例患者血清中ANA从阴性转化为阳性，ANA滴度或ANA特异性发生变化。在这6例患者中，2例诊断为肝细胞癌，1例诊断为转移性肝癌，1例正在接受干扰素治疗丙型肝炎。推测慢性肝病患者ANA的变化可能与肝癌的发展或干扰素治疗有关。在对合并原发性肝癌和不合并原发性肝癌的慢性肝病患者作为抗体靶点的自身抗原谱的比较研究中，非肌球蛋白在3例非肝癌的慢性丙型肝炎患者中被鉴定为自身抗原。另一方面，2例肝癌患者检测到抑瘤基因产物p53抗体，无癌慢性肝病患者未检测到p53抗体。慢性肝病伴肝癌与不伴肝癌患者自身抗原谱可能存在一定差异。

DNA topoisomerase II was newly identified as one of autoantigens which were reactive with antinuclear antibodies (ANAs) in patients with primary liver cancer. Another novel autoantigen that was a target of ANA from liver cancer, a 120 kilodalton nucleolar protein, has been characterized. That was shown to be localized in the dense fibrillar region of the nucleolus. Molecular nature of the protein has been currently under investigation with molecular cloning technique.From prospective study with 587 patients with chronic liver disease, six patients showed seroconversion of ANA from negative to positive, changes in ANA titers or ANA specificities. Of these 6 patients, two were diagnosed as having hepatocellular carcinoma, one as having metastatic liver cancer, and one was under interferon therapy for hepatitis C.It was speculated that changes in ANA in patients with chronic liver disease might be associated with development of liver cancer or interferon therapy.In the study of comparison of the spectrum of autoantigens which were targets of antibodies in chronic liver disease patients with or without primary liver cancer, non-muscle myosin was identified as autoantigen in 3 patients exclusively with chronic hepatitis C without liver cancer. On the other hand, antibodies to tumor suppresser gene product, p53, was detected in 2 patients with hepatocellular carcinoma and none in chronic liver disease without cancer. There might be certain difference in the spectrum of autoantigensin chronic liver disease patients with or without liver cancer.