Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membranous nephropathy, a disease characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane, is the most common cause of idiopathic nephrotic syndrome in Caucasian adults. In the rat model described by Heymann in 1959, the target antigen of antibodies is megalin, a multiligand receptor expressed in the rat glomerulus but absent from the human glomerulus. In the past few years, two major antigens have been identified in human membranous nephropathy. The first is neutral endopeptidase, the alloantigen involved in neonatal cases of membranous nephropathy that occur in newborns from neutral endopeptidase-deficient mothers. The second is the type-M phospholipase A2 receptor (PLA(2)R), the first autoantigen identified in idiopathic membranous nephropathy in the adult. Megalin, neutral endopeptidase, and PLA(2)R are all expressed on the podocyte surface where they serve as targets for circulating antibodies, which lead to in situ immune complex formation, complement activation, and proteinuria. The recent discovery of neutral endopeptidase and PLA(2)R provides new tools for monitoring human disease activity and should be of value in designing new antigen-driven therapeutic strategies.
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PMID:Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy. 2018 38

1. embranous nephropathy is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. 2. In the rat model described by Heymann in 1959, the target antigen of antibodies is megalin, a multiligand receptor expressed in the rat glomerulus but absent from the human glomerulus. 3. In recent years, two major antigens have been identified in human membranous nephropathy (MN). The first is neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of MN that occur in newborns from NEP-deficient mothers. The second is the M-type phospholipase A(2) receptor (PLA(2) R), the first autoantigen identified in idiopathic MN in the adult. Megalin, NEP and PLA(2) R are all expressed on the podocyte surface, where they can serve as targets for circulating antibodies, leading to in situ immune complex formation, complement activation and proteinuria. 4. In addition to podocyte antigens, we recently showed that some patients with childhood MN had both circulating cationic bovine serum albumin (BSA) and anti-BSA antibodies, with BSA being present in immune deposits. This suggests that food antigens may be involved in MN through charge-dependent binding to the anionic glomerular capillary wall and in situ formation of immune complexes.
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PMID:Advances in membranous nephropathy: success stories of a long journey. 2138 32

Over the past few years, considerable advances have been made in our understanding of the molecular pathomechanisms of human membranous nephropathy, inspired by studies of Heymann nephritis, a faithful experimental model of this disease. This research led to the identification of neutral endopeptidase, the M-type receptor for secretory phospholipase A(2) (PLA(2)R1) and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in alloimmune neonatal, adult 'idiopathic' and early-childhood membranous nephropathy, respectively. A genome-wide association study has provided further evidence for a highly significant association between PLA2R1 and HLA-DQA1 loci and idiopathic membranous nephropathy in patients of white ancestry. Additional antibody specificities for cytoplasmic antigens have also been identified, but their pathogenic role is uncertain. The time has come to revisit the spectrum of membranous nephropathies based on the newly identified antigen-antibody systems that should be considered as molecular signatures of the disease and that challenge the uniform histological definition. These signatures will soon have a major impact on patient care.
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PMID:Pathogenesis of membranous nephropathy: recent advances and future challenges. 2237 Dec 47

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 (PLA2R), 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 HLA-DQ, HLA-DR, and PLA2R1, 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.
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PMID:Molecular Pathogenesis of Membranous Nephropathy. 3162 60