Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis
Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis
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DOI：
10.1002/hep.20172
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发表时间：
2004-05-01
期刊：
影响因子：
13.5
通讯作者：
Treichel, U
中科院分区：
文献类型：
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作者：
Hilgard, P;Schreiter, T;Treichel, U
晚期酒精性肝病患者的溶血是一个常见的临床问题，并表明预后不良。在许多情况下，溶血的病因仍然未知。我们观察了三名酒精性肝病患者，患有严重的溶血性贫血，需要多次输血。类固醇治疗无效，两名患者死亡。所有患者的血清中都有可溶性的人去唾液酸糖蛋白受体（s-ASGP-R）变体，以及针对该受体的高滴度自身抗体（抗ASGP-R）。因此，对60例酒精性肝病患者的检查显示，酒精性肝硬化（ALC）患者中s-ASGP-R（36%）和抗ASGP-R（27%）的发生率高于病毒性肝炎所致肝硬化患者。对来自ALC患者和健康供体的红细胞进行了体外溶血的潜在病因学研究。分离的ASGP-R而非抗ASGP-R优先结合于血型A1的红细胞表面，并引起剂量依赖性凝集和溶血，而使用血型B的红细胞时这种现象要低得多，而使用血型O-红细胞时几乎不存在。此外，凝集和溶血只发生在ALC患者的红细胞或神经氨酸酶预处理后的细胞。ASGP-R诱导的凝集和溶血作用可被ASGP-R竞争性抑制剂去唾液酸胎球蛋白阻断。总之，我们的研究结果表明，酒精性肝病患者溶血的一种新的，非免疫机制，通过凝集介导的可溶性变体的人去唾液酸糖蛋白受体和机械剪切力。
Hemolysis in patients with advanced alcoholic liver disease is a common clinical problem and indicates an unfavorable prognosis. In many cases, the etiology of the hemolysis remains unknown. We observed three patients with alcoholic liver disease, suffering from severe hemolytic anemia, requiring multiple blood transfusions. Steroid therapy was ineffective and two of the patients died. All patients had a soluble variant of the human asialoglycoprotein receptor (s-ASGP-R) in their serum, as well as high titers of autoantibodies against this receptor (anti-ASGP-R). Consecutively, examination of 60 patients with alcoholic liver disease revealed a high incidence for s-ASGP-R (36%) and anti-ASGP-R (27%) in patients with alcoholic liver cirrhosis (ALC) compared to patients with cirrhosis due to viral hepatitis. The potential etiology of hemolysis was studied in vitro on erythrocytes from patients with ALC and from healthy donors. Isolated ASGP-R but not anti-ASGP-R bound to the surface of erythrocytes preferentially of blood group A1 and caused dose-dependent agglutination and hemolysis, while this phenomenon was much lower using erythrocytes of the blood group B and almost absent with blood group O-erythrocytes. Furthermore, agglutination and hemolysis only occurred in erythrocytes from ALC-patients or after the pretreatment of cells with neuraminidase. ASGP-R induced agglutination and hemolysis was blocked by the competitive ASGP-R inhibitor asialofetuin. In conclusion, our results indicate a new, non-immunological mechanism for hemolysis in patients with alcoholic liver disease, mediated through agglutination by a soluble variant of the human asialoglycoprotein receptor and mechanical shear stress.