Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease

Am J Kidney Dis. 2014 Feb;63(2):289-93. doi: 10.1053/j.ajkd.2013.08.032. Epub 2013 Nov 1.


Autoantibodies against a constituent of the glomerular basement membrane (GBM), the α3-chain of type IV collagen, can cause both rapidly progressive glomerulonephritis and alveolar hemorrhage, referred to as anti-GBM disease or Goodpasture disease. Anti-GBM antibodies generally are of immunoglobulin G subclass 1 (IgG1) and can in most cases readily be detected in the circulation using enzyme-linked immunosorbent assays (ELISAs). We report 4 cases in which anti-GBM ELISA yielded negative or borderline results despite life-threatening disease. All 4 patients had positive results by IgG4 anti-GBM ELISA and all had undetectable antineutrophil cytoplasmic antibody. All cases were confirmed with kidney biopsy. Two of the patients showed higher signal in anti-GBM ELISA when using a nondenaturing coating buffer. All 4 were young women with severe alveolar hemorrhage and favorable renal outcome, suggesting that patients with predominance of IgG4 autoantibodies may constitute a distinct subgroup of anti-GBM disease. We conclude that patients with idiopathic alveolar hemorrhage can have anti-GBM disease detected by only IgG subclass-specific tests or kidney biopsy.

Keywords: Anti–glomerular basement membrane (anti-GBM); Goodpasture disease; immunoglobulin G4 (IgG4).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Glomerular Basement Membrane Disease / blood*
  • Anti-Glomerular Basement Membrane Disease / diagnosis*
  • Anti-Glomerular Basement Membrane Disease / immunology
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood*
  • False Negative Reactions
  • Female
  • Humans
  • Immunoassay / methods
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood*
  • Young Adult


  • Autoantibodies
  • Immunoglobulin G
  • antiglomerular basement membrane antibody