Fleuren G J, Hoedemaeker P J
Clin Exp Immunol. 1980 Aug;41(2):218-24.
Autologous immune complex glomerulonephritis, an established experimental model of membranous glomerulopathy in man, has been used to investigate the effect of various drugs on its course. Because immunosuppressive or anti-inflammatory drugs are reported to have little or no effect on autologous immune complex glomerulonephritis a combination of cyclophosphamide, azathioprine and prednisolone was used in this study. Since in this glomerular disease free-circulating anti-FxlA antibody has pathogenetic significance special attention was paid to the effect of triple-drug treatment on the anti-FxlA serum titres and the relation between these titres, deposition of immune aggregates in the glomerular basement membrane and the occurrence of proteinuria. It was found that triple-drug treatment could prevent completely deposition of immune aggregates in the glomeruli as well as development of proteinuria when it was started simultaneously with the immunization procedure. If triple-drug treatment was started as the moment when immune deposits appeared along the glomerular basement membrane, a decrease in serum titre of autologous anti-FxlA antibody, diminished deposition of immune aggregates along basement membranes and a significant decrease of proteinuria were found. In later stages of the disease when proteinuria was fully developed, no beneficial effect of triple-drug treatment could be demonstrated. It is concluded that the beneficial effect of triple-drug treatment on early stages of autologous immune complex glomerulonephritis is caused by a decrease in the level of free-circulating anti-FxlA antibody.
自体免疫复合物性肾小球肾炎是一种公认的人类膜性肾小球病实验模型,已被用于研究各种药物对其病程的影响。由于据报道免疫抑制或抗炎药物对自体免疫复合物性肾小球肾炎几乎没有作用或根本没有作用,因此本研究使用了环磷酰胺、硫唑嘌呤和泼尼松龙的联合用药。由于在这种肾小球疾病中,游离循环的抗FxlA抗体具有致病意义,因此特别关注三联药物治疗对抗FxlA血清滴度的影响,以及这些滴度、免疫复合物在肾小球基底膜中的沉积与蛋白尿发生之间的关系。研究发现,三联药物治疗在与免疫程序同时开始时,可以完全防止免疫复合物在肾小球中的沉积以及蛋白尿的发展。如果在免疫沉积物沿肾小球基底膜出现时开始三联药物治疗,则会发现自体抗FxlA抗体的血清滴度降低、免疫复合物沿基底膜的沉积减少以及蛋白尿显著减少。在疾病的后期,当蛋白尿充分发展时,三联药物治疗没有显示出有益的效果。得出的结论是,三联药物治疗对自体免疫复合物性肾小球肾炎早期的有益作用是由游离循环的抗FxlA抗体水平降低引起的。