Target antigens and nephritogenic antibodies in membranous nephropathy: of rats and men

Semin Immunopathol. 2007 Nov;29(4):445-58. doi: 10.1007/s00281-007-0091-2. Epub 2007 Sep 26.


Membranous nephropathy, a disease characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane, is the most common cause of idiopathic nephrotic syndrome in white adults. In the rat model of Heymann nephritis, the target antigen of antibodies is megalin, a multiligand receptor expressed at the podocyte cell surface. This review summarizes key findings provided by this experimental model and by our discovery of neutral endopeptidase being the alloantigen involved in neonatal cases of membranous nephropathy. We discuss the role of alloimmunization as a new mechanism of renal disease and the approach that we use to identify new podocyte antigens. We also summarize current knowledge on the mechanism of proteinuria, with special emphasis on the role of complement. In conclusion, substantial progresses have been made in understanding molecular mechanisms of membranous nephropathy, which should lead to novel therapeutic approaches.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glomerular Basement Membrane / immunology*
  • Glomerular Basement Membrane / pathology
  • Glomerulonephritis, Membranous / immunology*
  • Glomerulonephritis, Membranous / pathology
  • Humans
  • Isoantigens / immunology*
  • Low Density Lipoprotein Receptor-Related Protein-2 / immunology*
  • Neprilysin / immunology*
  • Podocytes / immunology*
  • Podocytes / pathology
  • Proteinuria / immunology
  • Proteinuria / pathology
  • Rats
  • Syndrome


  • Isoantigens
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Neprilysin