Abstract
We characterized the glomerular antigen of membranous nephropathy (MN) in a child with the trial of MN, proximal renal tubular basement membrane autoantibody (TBMAb)-associated interstitial nephritis (ITN), and Fanconi syndrome. Granular staining was demonstrated for human gp600 in the vicinity of immune deposits of MN along glomerular capillary loops, using a monospecific polyclonal antibody to human gp600 by indirect immunofluorescence. However, no staining was observed in the MN deposits for receptor-associated protein. Membranous nephropathy preceded the development of TBMAbs, ITN, and Fanconi syndrome by 1 year, showing that the MN lesion does not result from the initial immunological injury to the tubulointerstitium, as postulated earlier. We confirmed the reactivity of TBMAbs with the recently deseribed rabbit 58-kilodalton (kDa) tubular basement membrane antigen (TBMAg). However, this is the first report to show reactivity of these antibodies with the human 58-kDa protein. Also, we found that TBMAg is comprised of a single protein band of 58 kDa, unlike the previously described combination of two protein bands (58 kDa and 175 kDa). In this patient, following prednisone treatment, the TBMAbs became undetectable, and the nephrotic syndrome and Fanconi syndrome resolved, thus suggesting a causal role of TBMAbs in the pathogenesis of Fanconi syndrome. We postulate that in this rare disorder, renal lesions result from an autoimmune response to the 58-kDa TBMAg and possibly to gp600, and that the predisposition to autoimmunity is genetically linked to the HLA B7 serotype.
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References
Lehman DH, Wilson CB, Dixon FJ (1975) Extraglomerular immunoglobulin deposits in human nephritis. Am J Med 58:765–786
Morel-Maroger L, Kourilsky O, Mignon F, Richet G (1974) Antitubular basement antibodies in rapidly progressive post-streptococcal glomerulonephritis: report of a case. Clin Immunol Immuopathol 2:185–194
Makker SP (1980) Tubular basement membrane antibody-induced interstitial nephritis in systemic lupus erythematosus. Am J Med 69:949–952
Levy M, Gagnadoux M-F, Beziau A, Habib R (1978) Membranous glomerulonephritis associated with anti tubular and anti alveolar basement membrane antibodies. Clin Nephrol 10:158–165
Tung KSK, Black WC (1975) Association of renal glomerular and tubular immune complex disease and antitubular basement membrane antibody. Lab Invest 32:696–700
Wood EG, Brouhard BH, Travis LB, Cavallo T, Lynch RE (1982) Membranous glomerulopathy with tubular dysfunction and linear tubular basement membrane IgG deposition. J Pediatr 101:414–417
Levy M, Guesry P, Loirat C, Dommergues JP, Nivet H, Habib R (1979) Immunologically mediated tubulo-interstitial nephritis in children. Contrib Nephrol 16:132–140
Katz A, Fish AJ, Santamaria P, Nevins TE, Youngki K, Butkowski RJ (1992) Role of antibodies to tubulointerstitial nephritis antigen in human anti-tubular basement membrane nephritis associated with membranous nephropathy. Am J Med 93:691–698
Heymann W, Hackel DB, Harwood J, Wilson SGF, Hunter JLP (1959) Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med 100:660–664
Alousi MA, Post RS, Heyman W (1969) Experimental autoimmune nephrosis in rats. Morphogenesis of the glomerular lesion: immunohistochemical and electron microscopic studies. Am J Pathol 54:47–71
Makker SP (1978) Evidence that the antigen of autologous immune complex glomerulonephritis of rats is mannose or glucose containing glycoproteins (abstract). Kidney Int 14:714
Makker SP (1980) Evidence that the antigen of autologous immune complex glomerulonephritis of rats is a mannose or glucose containing glycoprotein. Proc Soc Exp Biol Med 163:95–99
Makker SP, Singh AK (1982) Biochemical analysis of nephritogenic rat kidney tubular membrane fraction (Fx1A) (abstract). Fed Proc 41:1159
Kerjaschki D, Farquhar MG (1982) Identification of a membrane glycoprotein from kidney brush borders as the pathogenic antigen of Heymann nephritis (abstract) Fed Proc 41:692
Makker SP, Singh AK (1984) Characterization of the antigen (gp600) of Heymann nephritis. Lab Invest 50:287–293
Kerjaschki D, Farquhar MG (1982) Identification of a membrane glycoprotein from kidney brush border as the pathogenic antigen of Heymann's nephritis. Proc Natl Acad Sci USA 79:5557–5561
Kounnas MA, Argraves WS, Strickland DK (1992) The 39-kDa receptor associated protein interacts with two members of the low density lipoprotein receptor family, α2-macroglobulin receptor and glycoprotein 330. J Biol Chem 267:21162–21166
Willnow TE, Goldstein JL, Orth K, Brown MS, Herz J (1992) Low density lipoprotein receptor-related protein and gp330 bind similar ligands, including plasminogen activator-inhibitor complexes and lactoferrin, an inhibitor of chylomicron remnant clearance. J Biol Chem 267:26172–26180
Kounnas MZ, Chappell DA, Strickland DK, Argraves WS (1993) Glyprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro. J Biol Chem 268:14176–14181
Moestrup SK, Nielsen S, Andreasen P, Jorgensen KE, Nykjaer A, Roigaard H, Gliemann J, Christensen EI (1993) Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator-plasminogen activator inhibitor type-1 complexes. J Biol Chem 268:16564–16570
Saito A, Pietromonaco S, Kwor-Chieh Loo A, Gist Farquhar M (1994) Complete cloning and sequencing of rat gp330/“meaglin”, a distinctive member of the low density lipoprotein receptor gene family. Proc Natl Acad Sci USA 91:9725–9729
Edgington TS, Glassock RJ, Dixon FJ (1967) Autologous immune complex pathogenesis of experimental allergic glomerulonephritis. Science 155:1432–1433
Grupe WE, Kaplan MH (1969) Demonstration of an antibody to proximal tubular antigen in the pathogenesis of experimental autoimmune nephrosis in the rat. J Lab Clin Med 74:400–409
Kerjaschki D, Farquhar MG (1983) Immunocytochemical localization of Heymann nephritis antigen (gp330) in glomerular epithelial cells of normal Lewis rats. J Exp Med 157:667–686
Kanalas JJ, Makker SP (1991) Identification of a 45KD protein homologous to the α2-macroglobulin receptor associated protein that binds to the Heymann nephritis autoantigen (abstract). J Am Soc Nephrol 2:547
Kanalas JJ, Makker SP (1993) Analysis of a 45 kDa protein that binds to the Heymann nephritis autoantigen gp330. J Biol Chem 268:8188–8192
Strickland DK, Ashcom JD, Williams S, Battey F, Behre E, McTigue K, Battey JF, Argraves WS (1991) Primary structure of α2-macroglobulin receptor-associated protein. J Biol Chem 266:13364–13369
Kanalas JJ, Makker SP (1990) Isolation of a 330-kDa glycoprotein from human kidney similar to the Heymann nephritis autoantigen (gp600). J Am Soc Nephrol 1:792–798
Herz J, Goldstein JL, Strickland DK, Ho YK, Brown MS (1991) 39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/α2-macroglobulin receptor. J Biol Chem 266:21232–21238
Huang J, Makker SP (1995) Role of receptor-associated 39–45 kDa protein in active Heymann nephritis. Kidney Int 47:432–441
Makker SP, Makker DM (1986) A simple technique for detecting the antigen of Heymann nephritis in glomeruli by immunofluorescence. Clin Exp Immunol 64:615–622
Laemmli UK (1986) Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227:680–685
Makker SP, Kanalas JJ (1989) Course of transplanted Heymann nephritis kidney in normal host. Implications for the mechanism of proteinuria in membranous nephropathy. J Immunol 142:3406–3410
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Makker, S.P., Widstrom, R. & Huang, J. Membranous nephropathy, interstitial nephritis, and fanconi syndrome — glomerular antigen. Pediatr Nephrol 10, 7–13 (1996). https://doi.org/10.1007/BF00863427
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DOI: https://doi.org/10.1007/BF00863427