Gianella-Borradori A, Borradori L, Schneider P M, Gautier E, Späth P J
Department of Pediatrics, University Hospital, Lausanne, Switzerland.
Clin Immunol Immunopathol. 1990 Apr;55(1):41-55. doi: 10.1016/0090-1229(90)90067-z.
A family is described with two siblings who suffered at different times from a single episode of meningococcal meningitis by Neisseria meningitidis groups B and C, respectively. In the two subjects, hemolytically active fifth component of complement (C5) was not detectable and antigenic C5 was less than 0.05% and less than 0.7% of normal, respectively. Repletion of sera by purified human C5 (70 micrograms/ml) restored total complement hemolytic activities. The asymptomatic first degree family members had C5 levels compatible with a heterozygous state of C5 deficiency. C4 allotyping revealed an inherited partial deficiency (Q0) of C4A and C4B in the family with a combined C4AQ0 and C4BQ0 heterozygous condition in one and C4BQ0 heterozygosity in the other C5 deficient (C5D) subject. To our knowledge, this is the first human kindred with recognized combined C5 and C4 deficiency. No other defect of the humoral and cellular immune system was found in this family, including specific immune response to tetravalent meningococcal vaccine. The effect of partial C4 deficiency on classical pathway function was assessed by inhibition of immune precipitation (IIP) of forming bovine serum albumin (BSA)/anti-BSA immune complexes. Sera from all family members showed normal IIP values, with exception of the subject with combined partial deficiency in C4A, C4B, and complete deficiency in C5. Despite undetectable functional C5 in the C5D sera, the titration of the alternative pathway indicated intact but deficient hemolytic activities when rabbit erythrocytes (EC) were used as indicator cells in the presence of Mg2+ and EGTA in an end-point or kinetic assay. Preincubation of the two sera at 0 degrees C for 60 min with rabbit ECs reduced alternative pathway hemolytic activity by 24 and 100%, respectively. When rabbit ECs were replaced by guinea pig ECs no alternative pathway function could be measured. The results indicate that the apparent functional activity of the alternative pathway in C5D sera strongly depends on a factor(s) present in such serum and/or on the detection system used. We conclude that the two C5D individuals of the family reported here may not have sufficient C5 activity to provide efficient protection against Neisserial infections in conditions where complement functions beyond C3 opsonic activity are required in vivo.
本文描述了一个家庭，家中有两个兄弟姐妹，分别在不同时间感染了由B群和C群脑膜炎奈瑟菌引起的单发性脑膜炎球菌性脑膜炎。在这两名患者中，均未检测到具有溶血活性的补体第五成分（C5），抗原性C5分别低于正常水平的0.05%和0.7%。用纯化的人C5（70微克/毫升）补充血清可恢复总补体溶血活性。无症状的一级家庭成员的C5水平与C5缺陷的杂合状态相符。C4别型分析显示，该家族中存在遗传性的C4A和C4B部分缺陷（Q0），其中一名C5缺陷（C5D）患者为C4AQ0和C4BQ0联合杂合状态，另一名为C4BQ0杂合状态。据我们所知，这是首例被确认存在C5和C4联合缺陷的人类家族。该家族中未发现体液和细胞免疫系统的其他缺陷，包括对四价脑膜炎球菌疫苗的特异性免疫反应。通过抑制形成牛血清白蛋白（BSA）/抗BSA免疫复合物的免疫沉淀（IIP）来评估部分C4缺陷对经典途径功能的影响。除了C4A、C4B联合部分缺陷且C5完全缺陷的患者外，所有家庭成员的血清IIP值均正常。尽管C5D血清中功能性C5无法检测到，但在终点或动力学试验中，以兔红细胞（EC）为指示细胞，在Mg2+和乙二醇双乙胺四乙酸（EGTA）存在的情况下，替代途径的滴定显示溶血活性完整但有缺陷。将两份血清与兔EC在0℃预孵育60分钟后，替代途径溶血活性分别降低了24%和100%。当用豚鼠EC替代兔EC时，无法检测到替代途径功能。结果表明，C5D血清中替代途径的表观功能活性强烈依赖于该血清中存在的一种或多种因素和/或所使用的检测系统。我们得出结论，本文报道的该家族中的两名C5D个体可能没有足够的C5活性，无法在体内需要补体功能超过C3调理活性的情况下提供有效的抗奈瑟菌感染保护。
