Specificity and Nephrotoxicity of Heterologous Antibodies Directed Against Renal Basement Membranes

Abstract

Two immune sera have been raised in sheep against rabbit glomerular and tubular basement membranes, respectively (GBM and TBM). Their specificity was investigated by immunoabsorption and radioimmunoassay, and their nephrotoxicity was studied by injecting them into New Zealand rabbits. Both antisera reacted in vitro collagen and noncollagen-related glycopeptides. However, while the anti-GBM antiserum reacted preponderantly with GBM and TBM collagen which probably represent the antigen(s) shared by the two basement membranes, the anti-TBM antiserum was directed preferentially against the noncollagenous component of rabbit TBM. The anti-GBM antiserum induced in rabbits a diffuse extracapillary glomerulonephritis with linear fixation of autologous IgG and C₃ along the GBM. The anti-TBM antiserum also induced an extracapillary glomerulonephritis but in addition a focal tubular atrophy was seen and autologous IgG and C₃ were fixed along both GBM and TBM and glucosuria frequently occurred. These results suggested that the glomerular lesions induced by the two antisera were due to anticollagen antibodies while the tubulointerstitial lesions were due to antibodies directed against the noncollagenous portion of TBM.

Immunological Mechanisms of Interstitial Disease

“…Primary anti-TBM disease, in which there are linear deposits of immunoglobulin and circulating anti-TBM antibodies without evidence of glomerular antibody deposition, occurs occasionally in humans (26,311,312). In some of these cases, the tubular basement membrane antigen is 3M-1 (62), the same antigen that has been extensively studied in animal models of anti-TBM disease.…”