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Membranous nephropathy: an IgG4-mediated disease
1Division of Renal Medicine, St George's Hospital Medical School, London, UK.
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.
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.