Antigen size influences the type of glomerular pathology in chronic serum sickness

Chronic serum sickness was induced in four groups of Wistar rats by immunization with BSA, cationized BSA (cBSA), human IgG (HuIgG), or human IgM (HuIgM), followed by repeated intraperitoneal (i.p.) injection of the antigen used, to study the effect of the characteristics of an antigen on renal immunopathology. Renal tissue sampled 2, 4, 7, and 9 weeks after the start of the i.p. injections was examined by light-, immunofluorescence-, and electron-microscopy. Proteinuria was measured in urine collected over 24 h. All animals given BSA, cBSA, or HuIgG developed progressive renal disease characterized by initial deposition of antigen and rat Ig in the mesangium of rats given BSA or HuIgG, and minimal amounts in those given cBSA, followed by the appearance in the first instance of subendothelial deposits in the animals receiving BSA or HuIgG, and later subepithelial deposits in those given BSA, cBSA, or HuIgG. The appearance of immunoglobulin deposits along the glomerular capillary wall was associated with the onset of massive proteinuria reaching average levels of 450 mg/24 h for rats given BSA or cBSA, and 500 mg/24 h for those given HuIgG. Animals injected with HuIgM showed only mesangial deposits of human IgM and rat Ig without the development of proteinuria. Under light-microscopy, rats given BSA, cBSA, or HuIgM showed minimal abnormalities, whereas those receiving HuIgG showed transient but severe influx of granulocytes in glomeruli with the development of diffuse proliferative glomerulonephritis in association with a long-lasting phase characterized by subendothelially localized immune aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)