Experimental autoimmune Goodpasture's disease: a pathogenetic role for both effector cells and antibody in injury

Kidney Int. 2005 Feb;67(2):566-75. doi: 10.1111/j.1523-1755.2005.67113.x.


Background: Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury.

Methods: Active experimental autoimmune glomerulonephritis (EAG) was induced by immunization with alpha3-alpha5(IV)NC1 heterodimers in B cell intact C57BL/6 mice and B cell (mu chain-deficient) mice. Passive disease was induced by transferring sera from B cell intact and B cell deficient mice with EAG to RAG-1-/- mice (that lack adaptive immunity). Histologic and functional injury was studied.

Results: Despite the absence of B cells and immunoglobulin in B-cell-deficient mice, histologic and functional injury developed in mice immunized with alpha3-alpha5(IV)NC1, with T cells and macrophages in glomeruli. Injury occurred to a similar degree to that found in B-cell-intact mice. Transfer of sera from B-cell-intact mice with EAG containing antibodies (but not from B-cell-deficient mice with EAG) to RAG-1-/- mice induced linear immunoglobulin deposits on the glomerular basement membrane (GBM) and pathologic proteinuria.

Conclusion: Both cell-mediated and humoral effectors are capable of inducing renal injury in EAG. Given the similarity of the disease-initiating antigen in this model to the antigen in human anti-GBM glomerulonephritis, similar overlapping mechanisms are likely to operate in human disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / etiology*
  • Anti-Glomerular Basement Membrane Disease / immunology
  • Antibodies / physiology*
  • Antibodies / toxicity
  • Autoantibodies
  • B-Lymphocytes / physiology*
  • Glomerulonephritis / etiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proteinuria / etiology


  • Antibodies
  • Autoantibodies
  • antiglomerular basement membrane antibody