Trevillian P, Cameron J S
Clin Exp Immunol. 1979 Mar;35(3):338-49.
We studied the interaction of two different forms of immune glomerular damage occurring simultaneously: anti-glomerular basement membrane (GBM) antibody fixation and immune elimination of bovine serum albumin (BSA). 125I-radiolabelled BSA anti-BSA immune complexes, formed in response to a single small intravenous dose (150 mg/kg) of 125I BSA, did not cause proteinuria in control animals within 15 days, despite evidence of immune elimination of the antigen. Similarly, a small dose of nephrotoxic globulin (NTG)(3.0 mg/kg) did not cause immediate proteinuria in controls. Test animals received the BSA injection followed by the NTG injection 5, 7 or 9 days later. In this way, antibody fixed to glomerular basement membrane antigens at various times after BSA anti-BSA complexes first appeared in the circulation. Animals were killed on day 15. Fifteen of the eighteen test animals developed moderate to severe clinical nephritis. The onset of the nephritis coincided with BSA elimination irrespective of when the NTG was given. Greatly increased amounts of nonlinear immunofluorescent deposits were demonstrated in the glomeruli of test animals. We concluded that there was a marked synergistic effect between two forms of immune glomerular damage (i.e. that mediated by anti-GBM antibody and immune complexes), which appeared to be due to the increased deposition of complex material in the presence of active fixation of anti-GBM antibody. The relevance of this finding to human glomerulonephritis is discussed.
抗肾小球基底膜（GBM）抗体固定和牛血清白蛋白（BSA）的免疫清除。针对单次小剂量静脉注射（150 mg/kg）的125I BSA形成的125I放射性标记的BSA抗BSA免疫复合物，在15天内未在对照动物中引起蛋白尿，尽管有抗原免疫清除的证据。同样，小剂量的肾毒性球蛋白（NTG）（3.0 mg/kg）在对照动物中也未引起即刻蛋白尿。试验动物先接受BSA注射，然后在5、7或9天后接受NTG注射。通过这种方式，在BSA抗BSA复合物首次出现在循环中的不同时间，抗体固定在肾小球基底膜抗原上。在第15天处死动物。18只试验动物中有15只出现了中度至重度临床肾炎。肾炎的发作与BSA清除同时发生，与何时给予NTG无关。在试验动物的肾小球中发现大量非线性免疫荧光沉积物显著增加。我们得出结论，两种形式的免疫性肾小球损伤（即由抗GBM抗体和免疫复合物介导的损伤）之间存在明显的协同效应，这似乎是由于在抗GBM抗体的活性固定存在的情况下，复合物质的沉积增加所致。讨论了这一发现与人类肾小球肾炎的相关性。
