HMG1 protein and its receptor : their distribution and clinical significance

我们分离了高迁移率组（HMG）非组蛋白染色体蛋白1和2 （HMG1/HMG2）作为抗中性粒细胞胞浆抗体（ANCA）的靶抗原，并分析了这些自身抗体和自身抗原的作用。我们发现89%的自身免疫性肝炎患者存在抗hmg1 /HMG2抗体。基于最高的患病率和与疾病活动的相关性，这些抗体似乎是该疾病有用的临床标志物。我们还观察到HMG1以剂量依赖性的方式选择性地增强了胆管细胞系的增殖。采用多克隆和单克隆抗HMG1/HMG2抗体，建立了可溶性HMG1蛋白的ELISA检测体系，可检测血清HMG1水平高达10微克/毫升。我们发现，只要我们进行测试，致命性休克患者的血清HMG1就达到可检测水平。我们还建立了一种新的致死性小鼠模型，其中90%的肝血流被外科手术阻断。结扎后60小时所有小鼠死亡，结扎前血清HMG1水平显著升高。同时注射单克隆抗hmg1抗体可提高小鼠的存活率。综上所述，这些数据表明，HMG1蛋白可能在某种致命状态中发挥重要作用，干预血清HMG1水平可能是这种临界状态的新策略。

We isolated high mobility group (HMG) nonhisitone chromosomal proteins 1 and 2 (HMG1/HMG2) as target antigens of anti-neutrophil cytoplasmic antibody (ANCA), and have been analyzing the roles of those autoantibodies as well as the autoantigens. We found the existence of anti-HMG1/HMG2 antibodies in 89% of patients with autoimmune hepatitis. These antibodies seemed to be useful clinical markers in the disease based on the highest prevalence and the correlation with disease activity. We also observed that HMG1 selectively enhanced the proliferation of cholangial cell lines in a dose-dependent manner.We established an ELISA system for soluble HMG1 protein by using both polyclonal and monoclonal anti-HMG1/HMG2 antibody, which enabled us to test a serum HMG1 level as high as 10 micrograms/ml. We found that serum HMG1 reached a detectable level in fatal shock patients as long as we tested. We also established a novel fatal mouse model, in which 90% of the hepatic blood flow was blocked by a surgical procedure. All mice died 60 hr after the ligation, prior to which their serum HMG1 levels significantly increased. The survival rate increased by a simultaneous ip injection of monoclonal anti-HMG1 antibody. Taken together, these data indicates that HMG1 protein may play an important role in a certain fatal condition, and that the intervention of serum HMG1 levels may serve as a new strategy for such a critical state.