Leenaerts P L, Hall B M, Van Damme B J, Daha M R, Vanrenterghem Y F
Department of Nephrology, University Hospital Gasthuisberg, University of Leuven, Belgium.
Kidney Int. 1995 Jun;47(6):1604-14. doi: 10.1038/ki.1995.224.
The mechanisms of renal injury that result in proteinuria in active Heymann nephritis (AHN) remain unclear, though data suggest that in analogy of the passive form of the disease the membrane attack complex C5b-9 may be involved. AHN was induced in an inbred strain of PVG/c-rats that are totally deficient in the C6 component of complement and are unable to form the lytic C5b-9 complex, as well as in non-complement deficient PVG/c+ rats that are immunologic identical to the deficient strain. In both groups of animals comparably high titers of anti-Fx1A autoantibodies were found after three weeks and persisted at 40 weeks. Proteinuria was also similar in both groups, and was first evident at six weeks. High levels of urinary protein, ranging from 200 mg/24 hr to 500 mg/24 hr, were found after 10 weeks and persisted up to one year. Renal biopsy findings at various times post-immunization were identical in both groups, including immunofluorescence staining for Ig and C3 deposits, and also EM findings of subepithelial electron-dense deposits were not different. The injection of heterologous rabbit complement, that partially and temporarily restored the CH50 activity in PVG/c- rats did not alter or hasten the disease. Long-term follow-up showed that all rats in both groups continued to have severe proteinuria and that most animals died between 8 to 12 months after disease induction, without renal impairment. EM findings in serial biopsies demonstrated that the growth of the subepithelial deposits as measured by surface area occurred between weeks 4 and 12. A positive correlation (r = 0.94) between the size of the deposits and the level of proteinuria was found. These studies demonstrate that the membrane attack complex of complement does not play a major role in AHN. The relationship of the size of the immune deposits to the level of proteinuria suggests that the growth of the immune deposits on itself initiate secondary mechanisms that damage the permselective characteristics of the glomerular membrane.
在活动性海曼肾炎（AHN）中导致蛋白尿的肾损伤机制仍不清楚，不过有数据表明，与该疾病的被动形式类似，膜攻击复合物C5b - 9可能参与其中。在近交系PVG/c - 大鼠中诱导出AHN，这些大鼠完全缺乏补体C6成分，无法形成溶解性C5b - 9复合物，同时也在非补体缺陷的PVG/c + 大鼠中诱导出AHN，后者与缺陷品系具有相同的免疫特性。在两组动物中，三周后均发现了滴度相当高的抗Fx1A自身抗体，并且在40周时仍持续存在。两组的蛋白尿情况也相似，在六周时首次明显出现。10周后发现尿蛋白水平较高，范围在200毫克/24小时至500毫克/24小时之间，并持续长达一年。两组在免疫接种后不同时间的肾活检结果相同，包括Ig和C3沉积物的免疫荧光染色，而且上皮下电子致密沉积物的电镜检查结果也没有差异。向PVG/c - 大鼠注射异源兔补体，该补体部分且暂时恢复了CH50活性，但并未改变或加速疾病进程。长期随访表明，两组所有大鼠均持续存在严重蛋白尿，并且大多数动物在疾病诱导后8至12个月之间死亡，无肾功能损害。连续活检的电镜检查结果表明，上皮下沉积物表面积的增长发生在第4周和第12周之间。发现沉积物大小与蛋白尿水平之间存在正相关（r = 0.94）。这些研究表明，补体膜攻击复合物在AHN中不发挥主要作用。免疫沉积物大小与蛋白尿水平之间的关系表明，免疫沉积物自身的生长启动了损害肾小球膜选择通透性特征的继发机制。
