MEMBRANOUS NEPHROPATHY, INTERSTITIAL NEPHRITIS, AND FANCONI SYNDROME - GLOMERULAR ANTIGEN

We characterized the glomerular antigen of membranous nephropathy (MN) in a child with the triad of MN, proximal renal tubular basement memb rane 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 lo ops, using a monospecific polyclonal antibody to human gp600 by indire ct immunofluorescence. However, no staining was observed in the MN dep osits for receptor-associated protein. Membranous nephropathy preceded the development of TBMAbs, ITN, and Fanconi syndrome by 1 year, showi ng that the MN lesion does not result from the initial immunological i njury to the tubulointerstitium, as postulated earlier. We confirmed t he reactivity of TBMAbs with the recently described rabbit 58-kilodalt on (kDa) tubular basement membrane antigen (TBMAg). However, this is t he first report to show reactivity of these antibodies with the human 58-kDa protein. Also, we found that TBMAg is comprised of a single pro tein band of 58 kDa, unlike the previously described combination of tw o protein bands (58 kDa and 175 kDa). In this patient, following predn isone treatment, the TBMAbs became undetectable, and the nephrotic syn drome and Fanconi syndrome resolved, thus suggesting a causal role of TBMAbs in the pathogenesis of Fanconi syndrome. We postulate that in t his rare disorder, renal lesions result from an autoimmune response to the 58-kDa TBMAg and possibly to gp600, and that the predisposition t o autoimmunity is genetically linked to the HLA B7 serotype.