Relationship of the quality and quantity of circulating anti-BSA antibodies to the severity of glomerulonephritis in rats with chronic serum sickness.

Chronic serum sickness glomerulonephritis, induced in hyperimmunized rats by daily intravenous administration of bovine serum albumin, occurs in three stages, mild, moderate and severe, with abrupt onsets and distinctive features of kidney pathophysiology and immunopathology. We have studied the relationship between circulating anti-BSA antibodies and the severity of glomerulonephritis at each stage. The total amount of antibodies declined gradually during the course of disease, to low concentrations in the most severe stage of kidney inflammation. High levels of immune complexes were present in the circulation while precipitating antibodies were maintained, and rats remained in the mill stage of disease, exhibiting no abnormalities of kidney function and only mesangial immunopathology. The start of the moderate stage of chronic serum sickness, identified by proteinuria and the accumulation of immune deposits along the glomerular basement membrane, was associated with the disappearance of precipitating antibodies from circulation. With the onset of the severe stage of disease, marked by depressed glomerular filtration and sodium excretion, circulating antibodies of high affinity were no longer detected and circulating immune complex levels were only marginally elevated above normal. The experiments reported here demonstrate that, in chronic serum sickness glomerulonephritis of rats, transitions from one stage of kidney disease to another can be inferred from changes in the population of circulating antibodies. Kidney histopathology, therefore, can be predicted reliably from serological data alone.