Pathogenesis of Goodpasture syndrome: a molecular perspective

Semin Nephrol. 2003 Nov;23(6):522-31. doi: 10.1053/s0270-9295(03)00131-1.

Abstract

Goodpasture (GP) syndrome is a form of anti-glomerular basement membrane (GBM) disease, in which autoantibodies bind to alpha3(IV) collagen in GBM causing rapidly progressive glomerulonephritis and pulmonary hemorrhage. The conformational GP epitopes have been mapped to 2 regions within the noncollagenous (NC1) domain of the alpha3(IV) chain. Recently, we described the molecular organization of the autoantigen in the native alpha3alpha4alpha5(IV) collagen network of the GBM. The crystal structure of the NC1 domain has revealed how the GP epitopes are sequestered in the native GBM. Further insight into the pathogenesis of disease has been obtained from better animal models. These advances provide a foundation for the development of new specific therapies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Anti-Glomerular Basement Membrane Disease / physiopathology*
  • Antibody Specificity / immunology
  • Autoantibodies / analysis
  • Autoantibodies / biosynthesis*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / physiopathology
  • Basement Membrane / immunology
  • Basement Membrane / metabolism
  • Disease Models, Animal
  • Glomerulonephritis, Membranoproliferative / immunology*
  • Glomerulonephritis, Membranoproliferative / physiopathology
  • Humans
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / physiology
  • Mice
  • Models, Molecular
  • Molecular Biology

Substances

  • Autoantibodies