Nicholson-Weller A, March J P, Rosenfeld S I, Austen K F
Proc Natl Acad Sci U S A. 1983 Aug;80(16):5066-70. doi: 10.1073/pnas.80.16.5066.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired defect of bone marrow stem cells in which the affected clones produce erythrocytes (also granulocytes and platelets) with membranes that are abnormally sensitive to complement-mediated lysis. Abnormal erythrocytes (E) from patients with PNH (PNH-E) are 3-5 times more sensitive (type II PNH-E) or 15-25 times more sensitive (type III PNH-E) to lysis in vitro by human complement than normal E from unaffected individuals and the functionally normal E that arise from unaffected clones and the functionally normal E that arise from unaffected clones in PNH patients (type I PNH-E). After complement activation by either the classical or alternative pathway, abnormal amounts of C3b are deposited on the membranes of PNH-E compared with normal E, suggesting that the PNH-E membrane cannot regulate the events responsible for C3b deposition. Two proteins that decrease the stability of the classical and alternative pathway C3 convertases on target cells have been isolated from normal human E stroma: the 70,000 Mr decay accelerating factor of stroma (DAF) and the 250,000 Mr C3b receptor (C3bR). Specific immune precipitates of solubilized membranes from 125I-surface-labeled normal E demonstrate both proteins. In contrast, specific immune precipitates of PNH-E from three patients show C3bR but are deficient in DAF; type II PNH-E are relatively deficient and type III PNH-E are totally deficient in DAF. Antibody that neutralizes the activity of isolated DAF is adsorbed by intact normal E under conditions in which it is weakly adsorbed by type II PNH-E and not adsorbed by type III PNH-E. The deficiency of DAF antigen in PNH-E, as assessed by lack of immunoprecipitation and antibody adsorption, could explain the abnormal sensitivity of PNH-E to complement-mediated lysis and suggests that DAF may protect the membranes of normal E from damage resulting from autologous complement activation.
阵发性睡眠性血红蛋白尿（PNH）是一种骨髓干细胞的后天性缺陷，其中受影响的克隆产生的红细胞（也包括粒细胞和血小板），其细胞膜对补体介导的溶解异常敏感。与未受影响个体的正常红细胞以及PNH患者中未受影响克隆产生的功能正常的红细胞（I型PNH-E）相比，PNH患者的异常红细胞（PNH-E）在体外对人补体溶解的敏感性高3至5倍（II型PNH-E）或高15至25倍（III型PNH-E）。在经典途径或替代途径激活补体后，与正常红细胞相比，异常量的C3b沉积在PNH-E的细胞膜上，这表明PNH-E细胞膜无法调节负责C3b沉积的事件。从正常人红细胞基质中分离出两种可降低经典途径和替代途径C3转化酶在靶细胞上稳定性的蛋白质：70,000 Mr的基质衰变加速因子（DAF）和250,000 Mr的C3b受体（C3bR）。来自125I表面标记的正常红细胞的溶解膜的特异性免疫沉淀物显示这两种蛋白质都存在。相比之下，三名患者的PNH-E的特异性免疫沉淀物显示有C3bR，但缺乏DAF；II型PNH-E相对缺乏DAF，III型PNH-E完全缺乏DAF。在完整的正常红细胞能微弱吸附而III型PNH-E不吸附的条件下，中和分离出的DAF活性的抗体被完整的正常红细胞吸附。通过免疫沉淀和抗体吸附的缺乏评估，PNH-E中DAF抗原的缺乏可以解释PNH-E对补体介导的溶解的异常敏感性，并表明DAF可能保护正常红细胞的细胞膜免受自体补体激活造成的损伤。
