title: Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen.
abstract: Goodpasture's disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the alpha3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA-kappa antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the alpha1/alpha2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture's disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the alpha1/alpha2(IV) collagen chains as a novel target for nephritogenic antibodies.
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Dorin-Bogdan
authors.initials: DB
authors.lastname: Borza
authors.forename: Marcio F
authors.initials: MF
authors.lastname: Chedid
authors.forename: Selene
authors.initials: S
authors.lastname: Colon
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Lager
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
mesh_terms: D019867:Anti-Glomerular Basement Membrane Disease / Q000175:diagnosis* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D001323:Autoantibodies / Q000096:biosynthesis*; D001485:Basement Membrane / Q000737:chemistry / Q000276:immunology; D024042:Collagen Type I / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007126:Immunoglobulin Allotypes / Q000096:biosynthesis*; D007676:Kidney Failure, Chronic / Q000175:diagnosis; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D024042:Collagen Type I; D007070:Immunoglobulin A; D007126:Immunoglobulin Allotypes