title: Membranous nephropathy: A fairy tale for immunopathologists, nephrologists and patients.
abstract: This article reviews the considerable progress which has been made in the recent years in the understanding of the pathophysiology of membranous nephropathy, a model of organ-specific auto-immune disease. It shows how experimental models developed more than 30 years ago have led to the identification of several human antigens including neutral endopeptidase in the neonate, phospholipase A2 receptor, and thrombospondin 1 domain 7A in the adult, and cationic bovine serum albumin in children. Thanks to a successful GWAS performed in European Caucasians, the genetics of the disease begins to be understood. These groundbreaking findings already have a major impact on patients' care owing to the development of reliable ELISA and immunofluorescence test for the detection of PLA2R antibodies and of PLA2R antigen screening in biopsies. This review will tell the story from the careful clinical observation of cases to the most recent therapeutic perspectives which have been made possible by these advances. Advances in medical science often proceed by steps which are highly interdependent. New, groundbreaking findings with important clinical implications often result from the combination of faithful experimental models and careful clinical observations. This is well illustrated by the story of membranous nephropathy which started more than 50 years ago. It is remarkable that in this disease, the experimental models predicted the pathophysiology of the human glomerulopathy. The stories that we will tell in this article are aimed at young clinical investigators who are sometimes reluctant to embark on research projects. We hope that they will convince them that bedside research performed with intellectual curiosity and a bit of chance can lead to significant progress in clinical medicine.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France; INSERM, UMR_S 1155, Paris F-75020, France; AP-HP, Hôpital Tenon, Department of Nephrology and Dialysis, Paris F-75020, France. Electronic address: pierreronco@yahoo.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France; INSERM, UMR_S 1155, Paris F-75020, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
mesh_terms: D000328:Adult; D000486:Allergy and Immunology / Q000266:history; D001323:Autoantibodies / Q000096:biosynthesis; D002648:Child; D003167:Complement Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015260:Neprilysin / Q000235:genetics / Q000276:immunology*; D050199:Podocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D054507:Receptors, Phospholipase A2 / Q000235:genetics / Q000276:immunology*; D019699:Thrombospondins / Q000235:genetics / Q000276:immunology*; D057170:Translational Research, Biomedical / Q000266:history
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; C546399:THSD7A protein, human; D019699:Thrombospondins; D015260:Neprilysin
keywords: Antigens; Diagnosis; Membranous nephropathy; Podocyte