Immune complex glomerulonephritis and amyloidosis in Schistosoma japonicum infected rabbits

Abstract

Epidemiologically, the incidence of renal pathology in patients with chronic parasitic infections is higher than expected. In particular, schistosomiasis may have an association with renal failure. 24 New Zealand White rabbits were, therefore infected with 250 or 500 Schistosoma japanicum cercariae of the Philippine-Leyte strain and studied for eight months to determine if rabbits with long-term infections were suitable hosts for the study of schistosomal nephropathy. Clinical evidence for renal disease consisted of proteinuria, haematuria, and casts. Of the 18 surviving infected animals, six had trace amounts of protein in their urine, three had significant proteinuria ranging from 100 to 300 mg%, four exhibited haematuria and 14 were positive for the presence of proteinaceous cast formation. The clinical findings correlated with the histological data. Periodic open renal biopsies on a subgroup of the animals revealed no changes until about the sixth month. At eight months after infection, five (28%) of the 18 rabbits had amyloid deposits and 15 (83%) had some degree of renal change which included mild focal, diffuse intracapillary, and crescentic glomerulonephritis with mesangial and subendothelial complex trapping. Periodic-acid Schiff staining graphically demonstrated wire loops and tubular casts. Immunofluorescence showed that 15 (83%) of the infected animals exhibited diffuse mesangial and peripheral capillary wall deposition of IgG while 14 contained IgM (78%). The third component of complement was found in only five (28%) of the infected rabbits. Parasite antigen could not be detected in the glomeruli of any of the animals. Kidneys from age-matched controls were within normal limits. Electron microscopy of glomeruli from several animals demonstrated the presence of subendothelial and mesangial immune complex deposition similar to that seen in systemic upus erythematosus. These findings show that schistosomiasis japonica in the rabbit offers an excellent model system for studying not only the renal pathology associated with human schistosomiasis but also the pathogenesis of amyloidosis which is a frequent sequela observed in a variety of chronic inflammatory infections.