Membranous nephropathy, interstitial nephritis, and Fanconi syndrome : glomerular antigen

• Published in: Pediatric nephrology (Berlin, West) West), 1996-02, Vol.10 (1), p.7-13
• Main Authors: MAKKER, S. P, WIDSTROM, R, HUANG, J
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - blood; Anti-Inflammatory Agents - therapeutic use; Antigens - analysis; Antigens - isolation & purification; Autoantibodies - analysis; Autoantibodies - isolation & purification; Biological and medical sciences; Blotting, Western; Fanconi Syndrome - drug therapy; Fanconi Syndrome - immunology; Fanconi Syndrome - pathology; Fluorescent Antibody Technique, Indirect; Glomerulonephritis; Glomerulonephritis, Membranous - drug therapy; Glomerulonephritis, Membranous - immunology; Glomerulonephritis, Membranous - pathology; HLA Antigens - analysis; HLA Antigens - isolation & purification; Humans; Infant; Kidney Glomerulus - immunology; Kidney Glomerulus - pathology; Kidney Tubules, Proximal - immunology; Male; Medical sciences; Nephritis, Interstitial - drug therapy; Nephritis, Interstitial - immunology; Nephritis, Interstitial - pathology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Prednisone - blood; Prednisone - therapeutic use
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/BF00863427

We characterized the glomerular antigen of membranous nephropathy (MN) in a child with the triad 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 described 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 band (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.