title: Membranous Nephropathy: A Journey From Bench to Bedside.
abstract: Lessons from an animal model that faithfully resembles human membranous nephropathy (MN) have informed our understanding of the pathogenesis of this organ-specific autoimmune disease and common cause of nephrotic syndrome. After it was established that the subepithelial immune deposits that characterize experimental MN form in situ when circulating antibodies bind to an intrinsic podocyte antigen, it was merely a matter of time before the human antigen was identified. The M-type phospholipase A2 receptor 1 (PLA2R) represents the major target antigen in primary MN, and thrombospondin type 1 domain-containing 7A (THSD7A) was more recently identified as a minor antigen. Serologic tests for anti-PLA2R and kidney biopsy specimen staining for PLA2R show >90% specificity and 70% to 80% sensitivity for the diagnosis of primary MN in most populations. The assays distinguish most cases of primary MN from MN associated with other systemic diseases, and sequential anti-PLA2R titers are useful to monitor treatment response. A positive pretransplantation test result for anti-PLA2R is also helpful for predicting the risk for posttransplantation recurrence. Identification of target epitopes within PLA2R and the genetic association of primary MN with class II major histocompatibility and PLA2R1 variants are 2 additional examples of our evolving understanding of this disease.
authors.affiliation: Department of Medicine, Boston University Medical Center, Boston, MA.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Francis
authors.affiliation: Department of Medicine, Boston University Medical Center, Boston, MA.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Beck
authors.affiliation: Department of Medicine, Boston University Medical Center, Boston, MA. Electronic address: djsalant@bu.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Salant
mesh_terms: D001323:Autoantibodies / Q000032:analysis; D035843:Biomedical Research; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000235:genetics / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000276:immunology; D011379:Prognosis; D054507:Receptors, Phospholipase A2 / Q000276:immunology; D012008:Recurrence
chemical_list: D001323:Autoantibodies; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2
keywords: M-type phospholipase A(2) receptor 1 (PLA(2)R); Membranous nephropathy (MN); PLA2R1; class II major histocompatibility; epitope; genetic polymorphisms; nephrotic syndrome; organ-specific autoimmunity; post-transplant recurrent disease; thrombospondin type 1 domain-containing 7A (THSD7A)