Membranous nephropathy: from models to man

J Clin Invest. 2014 Jun;124(6):2307-14. doi: 10.1172/JCI72270. Epub 2014 Jun 2.

Abstract

As recently as 2002, most cases of primary membranous nephropathy (MN), a relatively common cause of nephrotic syndrome in adults, were considered idiopathic. We now recognize that MN is an organ-specific autoimmune disease in which circulating autoantibodies bind to an intrinsic antigen on glomerular podocytes and form deposits of immune complexes in situ in the glomerular capillary walls. Here we define the clinical and pathological features of MN and describe the experimental models that enabled the discovery of the major target antigen, the M-type phospholipase A2 receptor 1 (PLA2R). We review the pathophysiology of experimental MN and compare and contrast it with the human disease. We discuss the diagnostic value of serological testing for anti-PLA2R and tissue staining for the redistributed antigen, and their utility for differentiating between primary and secondary MN, and between recurrent MN after kidney transplant and de novo MN. We end with consideration of how knowledge of the antigen might direct future therapeutic strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibody Specificity
  • Autoantibodies / blood
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • Disease Models, Animal
  • Genetic Association Studies
  • Glomerulonephritis, Membranous / etiology*
  • Glomerulonephritis, Membranous / immunology
  • Glomerulonephritis, Membranous / therapy
  • Humans
  • Receptors, Phospholipase A2 / genetics
  • Receptors, Phospholipase A2 / immunology
  • Receptors, Phospholipase A2 / metabolism
  • Recurrence
  • Translational Research, Biomedical

Substances

  • Autoantibodies
  • Autoantigens
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2