title: The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey.
abstract: Ever since its first delineation as a distinct clinicopathologic entity in 1957, idiopathic membranous nephropathy (MN) has been the subject of intense laboratory and clinical investigation. The availability of laboratory models (particularly active and passive Heymann nephritis) of this disorder has been a boon to investigators. Concepts regarding the fundamental mechanisms of immune deposit formation, a sine qua non of idiopathic MN, have evolved and now are firmly established. Circulating autoantibodies (immunoglobulin G4 and immunoglobulin G1 subclasses) interacting with antigens native to or planted in the glomerular capillary wall at the podocyte cell membrane-basement membrane interface generally are regarded as the fundamental pathobiological mechanism. Thus, MN now is regarded as a podocytopathy. The immune deposits evoke an alteration in glomerular capillary permeability, probably through complement-mediated injury of the podocyte and its slit-pore membrane; however, cell-mediated immunity also may have a role, and the physical presence of immune deposits and basement membrane alterations also may participate. The exact nature of the autoantibody systems operative in human idiopathic MN is being uncovered rapidly. It is hoped that this 50-year odyssey will culminate in real progress in the diagnosis, prognosis, and therapy for the human disease.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. glassock@cox.net
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Glassock
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis; D015433:Glomerulonephritis, Membranous / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G