Studies on HRF 20, a novel membrane glycoprotein which restrict homologous complement reaction

我们开发了一种单克隆抗体，1F5，它能使人红细胞对同种人补体的溶血反应敏感。该抗原分子被鉴定为HRF20（20 kDa同源限制因子），可抑制C8和C9与细胞膜上的三分子中间补体复合物C5b67形成膜攻击复合物，在阵发性睡眠性血红蛋白尿症（PNH）患者异常红细胞中发现HRF20缺失。纯化的HRF 20吸附到异常PNH红细胞上重建了它们抵抗同源补体攻击的能力。我们发现了一个遗传性HRF20表达缺陷的患者。对患者HRF 20基因进行分析，发现患者HRF 20基因有2个位点有1个碱基缺失，免疫组化分析显示HRF 20不仅在血细胞上表达，而且在内皮细胞、肾细胞、神经雪旺细胞等也有表达，在胎儿细胞上也有明显表达，提示其可能具有保护胎儿的作用。我们还发现HIV感染者的CD8亮T淋巴细胞上HRF20的表达降低，甚至在AIDS或ARC症状出现之前。

We developed a monoclonal antibody, 1F5, which sensitizes human erythrocytes for hemolysis by homologous human complement. The antigenic molecule was identified to be HRF20 (20 kDa homologous restriction factor) which inhibit the reaction of C8 and C9 to form a membrane attack complex on C5b67, the trimolecular intermediate complement complex on cell membrane.HRF20 was found to be deficient on the abnormal erythrocytes of patients suffering from paroxysmal nocturnal hemoglobinuria (PNH). Adsorption of purified HRF20 on to the abnormal PNH erythrocytes reconstituted their ability to resist against homologous complement attack. We encountered to find a patient who is hereditary-deficient in HRF20 expression. Analysis of HRF20 gene of the patient revealed that one base deletion was found at 2 sites of the patient's HRF20 gene.Immunohistochemical analysis revealed that HRF20 is expressed not only on blood cells but also on endothelial cells, kidney cells, nerve Schwann cells, etc. HRF20 is also significantly expressed on fetal cells indicating that it would be playing a role to protect fetal, cells including nerve cell from membrane damage by complement.We also found that HRF20 expression was decreased on CD8 bright T lymphocytes from HIV-infected patients even before appearance of AIDS or ARC symptoms.