Transfer of Experimental Autoimmune Renal Cortical Tubular and Interstitial Disease in Guinea Pigs by Serum

Abstract

Guinea pigs injected with rabbit tubular basement membranes and Freund's adjuvant develop progressive renal cortical tubulointerstitial disease and deposit autoantibodies in their cortical tubular basement membranes. The identical, even fatal, disease may be produced in normal guinea pigs by a single intraperitoneal injection of serums obtained from guinea pigs with this tubulointerstitial disease, provided such serums contain sufficient amounts of autoantibodies against tubular basement membranes.

Multinucleated Giant Cells in Antiglomerular Basement Membrane Antibody-Induced Glomerulonephritis

“…These changes appear as early as 72 h following the injection of nephrotoxic globulin in rats [13]. An interpretation of these changes is that inflammatory mononuclear and giant cell infiltration can be mediated by humoral antibody [13,14], An experimental ocular in flammatory disease has also been produced passively in rabbits with high titers of antibody directed against lens protein [17], an inflammation that is granulomatous in nature. Furthermore, Kasdon and Schlossman [18] have produced a necrotizing, granulomatous response in pulmonary arteries of guinea pigs with high antibody to human serum albumin following the intra venous injection of albumin covalently linked to Sepharose beads, the authors suggesting that the local retention of antigen may play an important role in the subsequent evolution of granulomatous inflammation.…”

“…Autoimmune renal tubular disease in guinea pigs and rats is associated with antibodies directed against renal tubular basement membrane [13][14][15], and in both animals the disease has been transferred by serum alone [15,16], A characteristic feature of this disease is the appearance of macrophages, epithelioid cells, and muitinucleated giant cells surrounding atrophic tubules and basement-membrane fragments. These changes appear as early as 72 h following the injection of nephrotoxic globulin in rats [13].…”

Studies on the Pathogenesis of Experimental Autoimmune Renal Tubulointerstitial Disease in Guinea Pigs

“…22-23 days later the animals were killed. Kidney tissue was examined by light and immunofluorcscent microscopy [15]. Serum titers of TBM antibodies were done on strain 2 and/or Albany kidney sections [15].…”

“…RTD in guinea pigs is induced by au toantibodies reactive with the basement membrane of proximal tubules [15]. We have experimental evidence that the alterna tive pathway of complement participates in the accumulation of lymphocytes and ma crophages in the target tissue [8,9,13], A distinct strain difference in the induction of RTD has been observed [4,5].…”

“…Stud ies of a model of renal tubulointerstitial dis ease (RTD) in guinea pigs [14,15] have led to the identification of a previously unrec ognized association of antitubular base ment membrane (anti-TBM) autoantibod ies with renal lesions in cases of Fanconi's syndrome, methicillin-induccd nephritis, and poststreptococcal glomerulonephritis, after renal transplant, and in diphenylhydantoin-induced nephritis [1].…”