Characterization of basement membrane antigens present in the urine of normal and nephritic rabbits.

Abstract

Experimental glomerulonephritis was induced in rabbits with anti-rabbit glomerular basement membrane (RGBM) antisera raised in goats. The structural damage of the glomerular basement membrane (GBM) was characterized by excretion of basement membrane (BM) fragments into the urine which share determinants with enzyme-solubilized RGBM. Four BM antigens distinguished by molecular size, surface charge and antigenic structure were detected in the urine of nephritic animals. Quantitative determination showed an increased excretion of BM fragments into the urine of nephritic rabbits, corresponding to the development of renal injury. Fractionation studies of normal urine indicated the presence of trace amounts of two distinct BM antigens, immunologically identical or cross-reactive with two out of four BM antigens of acute nephritic urine. A severe glomerulonephritis developed in goats after injection with purified RGBM and is, in this sense, comparable to the effectiveness of heterologous BM in inducing kidney injury in sheep. Eluted antibodies from glomerulonephritic goat kidneys reacted with antigenic structures of the GBM obviously susceptible to collagenase treatment. On the other hand, urinary BM antigens failed to react with antibodies to tendon collagen suggesting that collagen is not an integral part of these antigens. The experimental evidence implicated the possibility of a nonspecific reaction between concentrated urine, or its chromatographic fractions, and goat sera, which may be confused with specific precipitates formed between urinary BM antigens and anti-RGBM antiserum.