The Role of Circulating Antigen in the Formation of Immune Deposits in Experimental Membranous Nephropathy

Publisher Website
Google Scholar
Abstract
To investigate the role of circulating antigen in the formation of subepithelial immune deposits in the Heymann rat model of membranous nephropathy, the renal uptake and site of renal deposition of intravenously injected renal tubular antigen (F .times. 1A) was studied, F .times. 1A, (15, 30, 60, and 600 .mu.g) radiolabeled with 125I, and bopvine serum albumin (BSA; 15 .mu.g) labeled with 131I were intravenously injected into naive rats. Plasma clearance and organ uptake of brush border antigens were determined. Of the injected F .times. 1A, 75% was cleared from the circulation by 1 hr as compared to 10% of the BSA. Uptake of F .times. 1A by heart, lung, and spleen was less than 1% at all doses studied. Renal uptake of F .times. 1A (29.8 .mu.g/g tissue) was greater than that for liver (4.75 .mu.g/g), spleen, heart, and lung (each less than 1 .mu.g/g tissue). Evalation of washed renal homogenate and isolated glomeruli confirmed specific tissue-associated F .times. 1A antigen. Direct immunofluorescence demonstrated deposits of F .times. 1A antigen along the glomerular capillary wall in animals injected with F .times. 1A. Small scattered electron dense deposits were demonstrated in the subepithelial space. Similar binding could be reproduced in vitro by incubating cryostat sections of normal rat kidney or isolated glomerculi with solubilized F .times. 1A antigens. Direct binding of a tubular antigen to a constituent of the glomerulus could initiate in situ immune complex formation, and may explain the variably demonstrable "cross-reactivity" of the Heymann antibody with the glomerular capillary wall.