Experimental Anti-GBM Nephritis
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An immunization of experimental animals with extracts of the glomerular basement membrane (GBM) mixed with Freund´s adjuvant produces serious glomerulonephritis. In this type of glomerulonephritis the antibodies and the complement factors are seen by immunofluorescence microscopy as a fine, linear band along the GBM (Steblay 1962, Unanue & Dixon 1967). This finding clearly demonstrates that the anti-GBM antibodies are attacking the GBM. The reaction between antibodies and antigen is followed by immune complex formation and inflammation, strongly suggesting that the kidney damage is caused by this reaction.
Counter-Argument
Again, serious glomerulonephritis is produced only if Freund´s adjuvant is used; an immunization alone does produce a linear deposition of antibodies and complement but it does not produce proteinuria or renal failure. As mentioned previously Freund´s adjuvant produces glomerulonephritis alone (Miettinen 1982). Therefore, the mentioned experiment is no proof that immunological reactions alone are causing glomerulonephritis. Most probably, Freund´s adjuvant sensitises the kidneys for immunological assaults. This is suggestive from the following experiment.
At first, rats were injected with Freund´s adjuvant alone. After 2-3 weeks rabbit anti-rat-GBM antibodies were injected into these rats in 1/20-1/15 of the amount required to produce glomerulonephritis in the Masugi model (see below). Control rats, that had not been pre-treated with Freund´s adjuvant, were injected with antibodies too. The pre-treated rats developed glomerulonephritis in two steps, just as in the Masugi nephritis (see below) and in the passive Heymann model, whereas no damage was seen in the rats that were not pre-treated with Freund´s adjuvant (Watson et al 1965).
Evidently, Freund´s adjuvant is an important co-factor in this experiment. The difference was not due to a stronger immunization of the rats that had been injected with Freund´s adjuvant because the amount of antibodies extracted from their kidneys was not larger than the amount of antibodies extracted from the kidneys of the rats in the control group. Again, the most reasonable conclusion is that Freund´s adjuvant predisposes the kidneys to immunological harassment (Ravnskov 1989).