Marder H K, Coleman T H, Forristal J, Beischel L, West C D
Kidney Int. 1983 May;23(5):749-58. doi: 10.1038/ki.1983.89.
The control of the amplification C3 convertase, C3b,Bb, of the serum complement system has been found to be defective in five members of a family spanning three generations. One of the five has membranoproliferative glomerulonephritis (MPGN) type III and another has mild idiopathic rapidly progressive glomerulonephritis. The defect is manifested by low serum concentrations of C3 and usually factor B with normal levels of the proteins which control the convertase, H and I. C3 nephritic factor (C3NeF) was not demonstrable. Enhanced C3 conversion was produced by the incubation of their serum at 37 degrees C for 30 min. This conversion was further accelerated by incubation after increasing the serum magnesium concentration by increments ranging from 0.25 to 1.9 mM. Incremental additions of H to serum depleted of H indicated that the amplification convertase of affected family members required more H for its inhibition than did that of normal subjects. This requirement was reduced by the addition of purified normal C3 but not by the addition of purified C3 of the propositus. It is postulated that affected family members are heterozygous for a gene producing an abnormal C3 which, as a constituent of the amplification convertase, C3b,Bb, confers resistance to H. Investigation of this apparently nephritogenic defect may provide insight into the pathogenesis of these glomerulonephritides.
血清补体系统的扩增性C3转化酶C3b,Bb的调控在一个三代家族的五名成员中被发现存在缺陷。五人中一人患有III型膜增生性肾小球肾炎（MPGN），另一人患有轻度特发性快速进展性肾小球肾炎。该缺陷表现为血清C3浓度低，通常还有因子B浓度低，而控制转化酶的蛋白质H和I水平正常。未检测到C3肾炎因子（C3NeF）。将他们的血清在37℃孵育30分钟可产生增强的C3转化。通过将血清镁浓度以0.25至1.9 mM的增量增加后孵育，这种转化进一步加速。向耗尽H的血清中逐步添加H表明，受影响家庭成员的扩增性转化酶比正常受试者的需要更多的H来抑制。通过添加纯化的正常C3可降低这一需求，但添加先证者的纯化C3则不能。据推测，受影响的家庭成员对于产生异常C3的基因是杂合子，该异常C3作为扩增性转化酶C3b,Bb的一个组成部分，赋予了对H的抗性。对这一明显的致肾炎缺陷的研究可能会为这些肾小球肾炎的发病机制提供见解。
