Rosenfeld S I, Baum J, Steigbigel R T, Leddy J P
J Clin Invest. 1976 Jun;57(6):1635-43. doi: 10.1172/JCI108434.
The first known human kindred with hereditary deficiency of the fifth component of complement (C5) was documented in the accompanying report. This study examines several biological properties of C5-deficient (C5D) human serum, particularly sera obtained from two C5D homozygotes. The proband, who has inactive systemic lupus erythematosus is completely lacking C5, while her healthy half-sister has 1-2% of normal levels. Both sera were severely impaired in their ability to generate chemotactic activity for normal human neutrophils upon incubation with aggregated human gamma-globulin or Escherichia coli endotoxin. This function was fully restored in the sibling's serum, and substantially improved in the proband's serum, by addition of highly purified human C5 to normal serum concentrations. Sera from eight family members who were apparently heterozygous for C5 deficiency gave normal chemotactic scores. The ability of C5D serum to opsonize Saccharomyces cerevisiae (baker's yeast) or Candida albicans for ingestion by normal neutrophils was completely normal. In addition, C5D serum was capable of promoting normal phagocytosis and intracellular killing of Staphylococcus aureus. The proband's serum was incapable of mediating lysis of erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria in both the sucrose hemolysia and acid hemolysis tests, and also lacked bactericidal activity against sensitized or unsensitized Salmonella typhi. The sibling's serum, containing only 1-2% of normal C5, effectively lysed S. typhi, but only at eightfold lower serum dilutions as compared to normals. These findings underscore the critical role of C5 in the generation of chemotactic activity and in cytolytic reactions, as opposed to a nonobligatory or minimal role in opsonization, at least for the organisms under study.
随附报告记录了首例已知的遗传性补体第五成分（C5）缺陷的人类家系。本研究检测了C5缺陷（C5D）人血清的几种生物学特性，特别是从两名C5D纯合子获得的血清。先证者患有非活动性系统性红斑狼疮，完全缺乏C5，而她健康的同父异母妹妹的C5水平为正常水平的1 - 2%。与聚合人γ球蛋白或大肠杆菌内毒素孵育后，两种血清在产生针对正常人中性粒细胞的趋化活性的能力上均严重受损。通过向正常血清浓度中添加高度纯化的人C5，同胞的血清中该功能完全恢复，先证者的血清中也有显著改善。八名明显为C5缺陷杂合子的家庭成员的血清趋化评分正常。C5D血清调理酿酒酵母（面包酵母）或白色念珠菌以供正常中性粒细胞吞噬的能力完全正常。此外，C5D血清能够促进对金黄色葡萄球菌的正常吞噬作用和细胞内杀伤。在蔗糖溶血试验和酸溶血试验中，先证者的血清均无法介导阵发性夜间血红蛋白尿患者红细胞的溶解，并且对致敏或未致敏的伤寒沙门氏菌也缺乏杀菌活性。同胞的血清仅含正常C5的1 - 2%，能有效溶解伤寒沙门氏菌，但与正常人相比，血清稀释倍数仅为正常的八分之一。这些发现强调了C5在趋化活性产生和细胞溶解反应中的关键作用，与在调理作用中（至少对于所研究的生物体）的非必要或最小作用形成对比。
