title: Enigma (partially) resolved: phospholipase A2 receptor is the cause of "idiopathic" membranous glomerulonephritis.
abstract: Membranous glomerulonephritis (MGN) is a very significant kidney disease. It is one of the frequent causes of heavy protein excretion in urine. MGN is thought to be an immune-mediated disease caused by glomerular deposition of antigen-antibody complexes. The pathogenic antigen, however, has been an enigma until recently. It was discovered in 2009 that phospholipase A2 receptor (PLA2R), a normal transmembrane protein in podocyte plasma membrane, is the antigen causing MGN. Within 5 yr of its discovery, this seminal finding has leaded to novel insights into the treatment of this disease including diagnosis, therapy, and prediction of outcome. This finding also paves the way for fundamental studies on how and why autoimmunity against PLA2R develops. The discovery of PLA2A as the cause of "idiopathic" MGN after a half century of speculation, followed by further fundamental insights with such an expedient and successful application in patient care, embodies the elegance of science at its junction with society. This perspective traces the story of this remarkable discovery.
authors.affiliation: Department of Pathology and Genomic Medicine, The Houston Methodist Hospital, Houston, Texas; Department of Pathology, Weill Medical College of Cornell University, New York, New York; and Departments of Pathology and Medicine, Baylor College of Medicine, Houston, Texas ltruong@tmhs.org.
authors.forename: Luan D
authors.initials: LD
authors.lastname: Truong
authors.affiliation: Department of Pathology, Weill Medical College of Cornell University, New York, New York; and.
authors.forename: Surya V
authors.initials: SV
authors.lastname: Seshan
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015433:Glomerulonephritis, Membranous / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D054507:Receptors, Phospholipase A2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D054507:Receptors, Phospholipase A2
keywords: PLA2R; membranous glomerulonephritis