Abstract
Two children with Alport's syndrome are described, who developed anti-glomerular basement membrane (GBM) antibody-mediated nephritis after renal transplantation. The reactivity of antibodies in their serum with collagenase-solubilized normal GBM was examined by SDS-PAGE with one- and two-dimensional immunoblotting. The specificity was compared with that of antibodies present in serum from a patient with Goodpasture's syndrome, and a mouse monoclonal antibody (MCA-P1), directed against the Goodpasture antigen. All reacted in a similar way with collagenase-solubilized GBM. Since abnormalities in the composition of the GBM are present in Alport's syndrome, it is proposed that differing antigen composition of GBM in the host compared with the donor kidney, together with transplant rejection, may have provoked the development of post-transplant anti-GBM antibodies.
Similar content being viewed by others
References
Wilson CB (1980) Individual and strain differences in renal basement membrane antigens. Transplant Proc 12:69–73
McCoy RC, Johnson HK, Stone WJ, Wilson CB (1982) Absence of nephritogenic GBM antigen(s) in some patients with hereditary nephritis. Kidney Int 21:642–652
Milliner DS, Pierides AM, Holley KE (1982) Renal transplantation in Alport's syndrome. Mayo Clin Proc 57:35–43
Kashtan C, Fish AJ, Kleppel M, Yoshioka K, Michael AF (1986) Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis. J Clin Invest 78:1035–1044
Teruel JL, Liaño F, Mampaso F, Moreno J, Serrano A, Quereda C, Ortuno J (1987) Allograft antiglomerular basement membrane glomerulonephritis in a patient with Alport's syndrome. Nephron 46:43–44
Shah B, First MR, Mendoza NC, Clyne DH, Alexander JW, Weiss MA (1988) Alport's syndrome: risk of glomerulonephritis induced by anti-glomerular-basement-membrane antibody after renal transplantation. Nephron 50:34–38
Savage COS, Pusey CD, Kershaw MJ, Cashman SJ, Harrison P, Hartley B, Turner DR, Cameron JS, Evans DJ, Lockwood CM (1986) The Goodpasture antigen in Alport's syndrome: studies with a monoclonal antibody. Kidney Int 30:107–113
Hoitsma AJ, Lier HJJ van, Wetzels JFM, Berden JHM, Koene RAP (1987) Cyclosporin treatment with conversion after three months versus conventional immunosuppression in renal allograft recipients. Lancet I:584–586
Feltkamp-Vroom TM, Balner H (1972) Glomerular basement membrane-reactive antibodies in anti-lymphocyte sera: in vitro and in vivo characteristics. Eur J Immunol 2:166–173
Bowman C, Lockwood CM (1985) Clinical application of a radioimmunoassay for autoantibodies to glomerular basement membrane. J Clin Lab Immunol 17:197–202
Westberg NG, Michael AF (1970) Human glomerular basement membrane, preparation and composition. Biochemistry 9:3837–3846
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Pollard JW (1984) Two-dimensional polyacrylamide gel electrophoresis of proteins. In: Walker JM (ed) Methods in molecular biology. Human Press, New Jersey, pp 81–96
Towbin H, Staehelin T, Gordon J (1978) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets and some applications. Proc Natl Acad Sci USA 76:4350–4354
Burnette WN (1981) Western blotting: electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gel to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein. Anal Biochem 112:194–200
Pressey A, Pusey CD, Dash A, Peters DK, Lockwood CM (1983) Production of a monoclonal antibody to autoantigenic components of human glomerular basement membrane. Clin Exp Immunol 54:178–184
Hawkes R, Niday E, Gordon J (1982) A dot-immunoblotting assay for monoclonal and other antibodies. Anal Biochem 119:142–147
Groth CG, Ringdén O (1984) Transplantation in relation to the treatment of inherited disease. Transplant 38:319–327
Noël LH, Gubler MC, Bobrie G, Savage COS, Lockwood CM, Grünfeld JP (1989) Inherited defects of renal basement membranes. In: Advances in nephrology, vol 18. Year Book Medical, Chicago, (pp 77–94)
Anand SK, Landing BH, Heuser ET, Olson DL, Grushkin CM, Lieberman E (1978) Changes in glomerular basement membrane antigen(s) with age. J Pediatr 92:952–953
Yoshioka K, Michael AF, Velosa J, Fish AJ (1985) Detection of hidden nephritogenic antigen determinants in human renal and nonrenal basement membranes. Am J Pathol 121:156–165
Wieslander J, Bygren P, Heinegard D (1984) Isolation of the specific glomerular basement membrane antigen involved in Goodpasture syndrome. Proc Natl Acad Sci USA 81:1544–1548
Wieslander J, Barr JF, Butkowski RJ, Edwards SJ, Bygren P, Heinegard D, Hudson BG (1984) Goodpasture antigen of the glomerular basement membrane: localization to noncollagenous regions of type IV collagen. Proc Natl Acad Sci USA 81:3838–3842
Butkowski RJ, Wieslander J, Wisdom BJ, Barr JF, Noelken ME, Hudson BG (1985) Properties of the globular domain of type IV collagen and its relationship to the Goodpasture antigen. J Biol Chem 260:3739–3747
Wieslander J, Langeveld J, Butkowski R, Jodlowski M, Noelken M, Hudson BG (1985) Physical and immunochemical studies of the globular domain of type IV collagen. Cryptic properties of the Goodpasture antigen. J Biol Chem 260:8564–8570
Wieslander J, Kataja M, Hudson BG (1987) Characterization of the human Goodpasture antigen. Clin Exp Immunol 69:332–340
Butkowski RJ, Langeveld JPM, Wieslander J, Hamilton J, Hudson BG (1987) Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem 262:7874–7877
Kleppel MM, Kashtan CE, Butkowski RJ, Fish AJ, Michael AF (1987) Alport familial nephritis. Absence of 28 kilodalton non-collagenous monomers of type IV collagen in glomerular basement membrane. J Clin Invest 80:263–266
Savage COS, Noël L-H, Crutcher E, Price RG, Grünfeld JP, Lockwood CM (1989) Hereditary nephritis: immunoblotting studies of the glomerular basement membrane. Lab Invest (in press)
Feingold J, Bois E, Chompret A, Broyer M, Gubler MC, Grünfeld JP (1985) Genetic heterogeneity of Alport syndrome. Kidney Int 27:672–677
Yoshioka K, Kleppel M, Fish AJ (1985) Analysis of nephritogenic antigens in human glomerular basement membrane by two-dimensional gel electrophoresis. J Immunol 134:3831–3837
Price RG, Wong M (1988) Heterogeneity of Goodpasture's antigen. J Pathol 156:97–99
Wong M, Lockwood MC, Savage COS, Price RG (1988) Study of the specificity of circulating autoantibodies to glomerular basement membrane (GBM) by two dimensional electrophoresis. In: Sternberg M, Gubler MC, Price RG (eds) Progress in basement membrane research: renal and related aspects. Libbey, London, pp 111–114
Fleming SJ, Savage COS, McWilliam LJ, Pickering SJ, Ralston AJ, Johnson RWG, Ackrill P (1988) Anti-GBM antibody mediated nephritis complicating transplantation in a patient with Alport's syndrome. Nephrol Dial Transplant 46:857–860
Michael AF (1987) Extracellular membranes of th glomerulus. In: Murakami K (eds) Recent advances in pediatric nephrology. Elsevier Biomedical, Amsterdam, pp 45–50
Flinter FA, Bobrow M, Chantler C (1987) Alport's syndrome or hereditary nephritis? Pediatr Nephrol 1:438–440
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
v. d. Heuvel, L.P.W.J., Schröder, C.H., Savage, C.O.S. et al. The development of anti-glomerular basement membrane nephritis in two children with Alport's syndrome after renal transplantation: characterization of the antibody target. Pediatr Nephrol 3, 406–413 (1989). https://doi.org/10.1007/BF00850217
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00850217