muramidase and Serum-Sickness

A wide variety of tests for the detection of circulating immune complexes (IC) has been proposed by different authors, but there is very little to no information concerning the performance of IC screening assays in samples known to contain in vivo-formed IC. The purpose of our investigation was to compare the behavior of a non-specific assay, the PEG-IgG screening test for IC, with an antigen-specific assay in serum samples sequentially obtained from rabbits to which we induced acute serum sickness. Five animals were used in the study; we were able to detect an increase of IC constituted by the heterologous antigen (human serum albumin) and corresponding antibodies in all, and in 4 animals the results of the PEG-IgG assay closely correlated with the results of the antigen-specific assay (rho values between 0.975 and 1.00). The 4 animals in which IC showed a definite peak by both assays developed proteinuria and IC deposits at the glomerular level, while the animal that failed to develop IC detectable by the PEG-IgG test remained normal throughout the study. These results demonstrate the ability of the PEG-IgG test to detect in vivo-formed IC and suggest that the IC detected by this test have pathogenic potential.

Topics: Acute Disease; Albuminuria; Animals; Antigen-Antibody Complex; Autoimmune Diseases; Disease Models, Animal; Immunoglobulin G; Longitudinal Studies; Muramidase; Polyethylene Glycols; Proteinuria; Rabbits; Serum Sickness

Using highly cationic polyethleneimine, alteration of glomerular anionic sites were evaluated ultrastructurally in two types of rat glomerulonephritis (GN); chronic serum sickness GN and heterologous (passive) or autologous (active) Heymann's GN. Daily i.v. injections of egg white lysozyme in physiologic saline into presensitized rats led to the formation of numerous mesangial and subepithelial deposits. In the non-proteinuric period in which immune deposits were localized predominantly in the mesangium, anionic sites of the laminae rarae and the epithelial cell coat were clearly observed. In the subsequent proteinuric period in which numerous subepithelial deposits were superimposed, a broad loss of anionic sites in the epithelial cell coat was seen. Splitting and focal loss of anionic sites on the lamina rara externa adjacent to the subepithelial deposits were commonly observed both in passive and active Heymann's GN and in lysozyme GN. These findings indicate that the subepithelial deposits are closely involved in the development of proteinuria by injuring the anionic sites, especially those on lamina rare externa of the glomerular basement membrane.

Topics: Animals; Anions; Antigen-Antibody Complex; Glomerulonephritis; Immunization; Kidney Glomerulus; Male; Microscopy, Electron; Muramidase; Proteinuria; Rats; Rats, Inbred Strains; Serum Sickness

Epimembranous glomerular deposition of circulating immune complexes in considered to be the pathogenesis of immune complex glomerulonephritis, based on experiments in serum sickness glomerulopathy. A subepithelial localization of immune aggregates, however, was never obtained after the intravenous injection of preformed immune complexes. Recent studies on heterologous immune complex glomerulonephritis provide evidence of in situ formation of subepithelial glomerular immune complex aggregates as a second pathogenetic mechanism. We investigated the existence of a comparable mechanism in a serum sickness model of glomerulonephritis. A passive immune complex glomerulopathy involving lysozyme/antilysozyme and bovine serum albumin (BSA)/anti-BSA was used to investigate this thesis. Alternating perfusion of a kidney with antigen and antibody resulted in a granular deposition of both components along the glomerular basement membrane (GBM). The deposits of immune aggregates were localized exclusively along the epithelial side of the GBM and were still present 3 days after the perfusion. Control perfusions with preformed immune complexes or with either BSA or anti-BSA alone did not result in subepithelial deposition. Conclusion. The alternating excess of antigen and antibody in the circulation might result in in situ formation of immune complexes localized at the epithelial side of the GBM.

Topics: Animals; Antibody Formation; Antigen-Antibody Complex; Female; Immune Complex Diseases; Kidney Glomerulus; Muramidase; Perfusion; Rats; Serum Albumin, Bovine; Serum Sickness