Membranous nephropathy: an IgG4-mediated disease

Membranous nephropathy is characterised by the deposition of immunoglobulin, predominantly of the IgG4 subclass, along the epithelial surface of the glomerular-basement membrane. Current models of pathogenesis usually assume in-situ immune-complex formation involving an as yet uncharacterised fixed glomerular antigen. I argue that the properties of IgG4 (inability to fix complement and therefore impaired clearance of IgG4-containing complexes; low affinity and therefore ability for IgG4-containing complexes to dissociate and traverse the glomerular-basement membrane) are compatible with a pathogenic mechanism that involves the deposition of circulating IgG4 immune complexes containing diverse antigens.