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

Chronic serum sickness was induced in four groups of Wistarrats by immunization with BSA, cationized BSA (cBSA), humanIgG (HuIgG), or human 1gM (HuIgM), followed by repeated intraperitoneal (i.p.) injection of the antigen used, to study the effectof the characteristics of an antigen on renal immunopathology.Renal tissue sampled 2, 4, 7, and 9 weeks after the start ofthe i.p. injections was examined by light-, immunofluorescence-,and electron microscopy. Proteinuna was measured in urine collected over 24 h. All animals given BSA, cBSA, or HuIgG developedprogressive renal disease character ized by initial depositionof antigen and rat Ig in the mesangium of rats given BSA orHuIgG, and minimal amounts in those given cBSA, followed bythe appear ance in the first instance of subendothelial depositsin the animals receiving BSA or HuIgG, and later subepi thelialdeposits in those given BSA, cBSA, or HuIgG. The appearanceof immunoglobulin deposits along the glomerular capillary wallwas associated with the onset of massive proteinuria reachingaverage levels of 450 mg/24 h for rats given BSA or cBSA, and500 mg/24 h for those given HuIgG. Animals injected with HuIgMshowed only mesangial deposits of human 1gM and rat Ig withoutthe development of proteinuria. Under light-microscopy, ratsgiven BSA, cBSA, or HuIgM showed minimal abnormalities, whereasthose receiving HuIgG showed transient but severe influx ofgranulocytes in glomeruli with the development of diffuse proliferativeglomerulonephritis in association with a long-lasting phasecharacterized by subendothel ially localized immune aggregates.No differences in the degree or type of the immune responsewere found either as measured by ELISA or double radial immunodiffusion. We conclude that the type of glomerular immunopathologyduring chronic serum sickness is partially dependent on thesize of the antigen used for induction of the disease.