Goodpasture's disease: Molecular architecture of the autoantigen provides clues to etiology and pathogenesis

  • Pedchenko V
  • Vanacore R
  • Hudson B
  • 27

    Readers

    Mendeley users who have this article in their library.
  • 15

    Citations

    Citations of this article.

Abstract

PURPOSE OF REVIEW Goodpasture's disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung, which induces rapidly progressive glomerulonephritis and pulmonary hemorrhage. The target antigen is the α3NC1 domain of collagen IV, which is expressed in target organs as an α345 network. Recent studies of specificity and epitopes of Goodpasture's autoantibodies and discovery of novel posttranslational modification of the antigen, a sulfilimine bond, provide further insight into mechanisms of initiation and progression of Goodpasture's disease. RECENT FINDINGS Analysis of the specificity of Goodpasture's autoantibodies revealed a distinct subset of circulating and kidney-bound antiα5NC1 antibody, which is associated with loss of kidney function. Structural integrity of the α345NC1 hexamer is stabilized by the novel sulfilimine crosslinks conferring immune privilege to the Goodpasture's autoantigen. Native antibodies may contribute to establishment of immune tolerance to autoantigen. Structural analysis of epitopes for autoantibodies and alloantibodies indicates a critical role of conformational change in the α345NC1 hexamer in eliciting an autoimmune response in Goodpasture's disease. SUMMARY Understanding of the quaternary structure of the Goodpasture's autoantigen continues to provide insights into autoimmune mechanisms that serve as a basis for development of novel diagnostic tools and therapies for Goodpasture's disease.

Author-supplied keywords

  • Goodpasture's disease
  • autoantibodies
  • autoantigen
  • collagen type IV
  • epitopes
  • glomerular basement membrane

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Vadim Pedchenko

  • Roberto Vanacore

  • Billy Hudson

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free