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Annual Review of Pathology: Mechanisms of Disease

Volume 15, 2020

Molecular Pathogenesis of Membranous Nephropathy

Abstract

Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLAR), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. The development of highly specific and sensitive assays of circulating antibodies has induced a paradigm shift in diagnosis and treatment monitoring. In addition, several interacting loci in , , and , as well as classical human leukocyte antigen (HLA)-D alleles have been identified as being risk factors, depending on a patient's ethnicity. Additionally, mechanisms of antibody pathogenicity and pathways of complement activation are now better understood. Further research is mandatory for designing new therapeutic strategies, including the identifying triggering events, the molecular bases of remission and progression, and the T cell epitopes involved.

Keyword(s): genome-wide association studies, GWAS, HLA-D risk variants, membrane attack complex of complement, neutral endopeptidase, phospholipase A2 receptor, PLA2R, thrombospondin domain-containing 7A, THSD7A
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2020-01-24
2024-04-25
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Molecular Pathogenesis of Membranous Nephropathy
Annual Review of Pathology: Mechanisms of Disease 15, 287 (2020); https://doi.org/10.1146/annurev-pathol-020117-043811
/content/journals/10.1146/annurev-pathol-020117-043811
/content/journals/10.1146/annurev-pathol-020117-043811
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