We report three patients, from two unrelated families, with anti-tubular basement membrane (TBM) antibody
nephritis associated with
membranous nephropathy. This rare disorder is characterized by
nephrotic syndrome, tubular dysfunction, and progression to
renal failure. Direct immunofluorescent studies in these patients revealed linear
IgG deposition along the proximal TBM, while circulating
antibodies reacting with proximal TBM but not with glomerular basement membrane were identified by indirect immunofluorescence. Sera from all three patients reacted by
enzyme-linked
immunosorbent assay and Western immunoblotting with purified 58-kd
tubulointerstitial nephritis (
TIN)
antigen isolated from TBM. Additional reactivity with a 175-kd component, which may be a higher-molecular-weight form of
TIN antigen, was observed by immunoblotting. Since recurrent
Fanconi syndrome was seen after
transplantation in one patient, anti-TBM
antibodies were removed by
plasmapheresis prior to
kidney transplantation in the other two patients. Neither patient has clinical evidence of recurrent anti-TBM
nephritis in the allograft despite the posttransplantation reappearance of anti-TBM
antibodies in the serum of one patient. Serologic and molecular HLA class I and class II polymorphism analysis has identified the presence of both
HLA-B7 and -DRw8
antigens in two unrelated affected individuals (0.3% expected frequency in the white population). We conclude that sera from patients with anti-TBM
nephritis associated with
membranous nephropathy react with 58-kd
TIN antigen previously implicated in the pathogenesis of primary anti-TBM
nephritis. This rare autoimmune disorder may be HLA associated with B7 and/or DRw8, providing susceptibility to the disease. Further investigation is needed to understand the pathogenesis of recurrent anti-TBM
nephritis in the renal allograft.