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)

Antibodies to neutral endopeptidase, a podocyte protein, are responsible for rare alloimmune neonatal membranous nephropathy that develops in children from neutral endopeptidase-deficient mothers. Neutral endopeptidase was the first podocyte antigen described in human membranous nephropathy. PLA2R1, the type-M receptor of soluble phospholipase A2, is a major target antigen in so-called idiopathic membranous nephropathy in adults. Antibodies to PLA2R1 are detected in 60 to 80% of patients before immunosuppressive treatment, and are only occasionally found in secondary membranous nephropathy. To date, they have not been detected in other pathological conditions and in healthy individuals. PLA2R1 and HLA-DQA1 gene variants defined by single nucleotide polymorphisms are strongly associated with idiopathic membranous nephropathy in patients of white ancestry, and can thus be considered as predisposing genes. In addition to their diagnostic value, anti-PLA2R1 antibodies can be used to monitor treatment. Immunization against cationic bovine serum albumin is a cause of early childhood membranous nephropathy. This finding points to a possible role of food and environmental antigens in membranous nephropathy. The newly identified antigen-antibody systems should be considered as molecular signatures challenging the uniform histological definition and having a major impact on patient care in a near future.
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PMID:[Idiopathic and secondary membranous nephropathies]. 2220 61

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 (MN) is a kidney disease characterized by deposition of immune complexes and complement on the outer aspect of the glomerular capillary wall. It is responsible for a loss of serum proteins in the urine and kidney failure. During the last ten years, considerable progress has occurred in the understanding of the molecular bases of the disease with the description of three distinct mechanisms in humans. In the neonatal allo-immune form, antibodies are directed against neutral endopeptidase (NEP), a podocyte antigen absent in the mothers who become immunized against this antigen expressed by placenta cells during pregnancy. NEP was the first podocyte antigen to be identified in MN. Most adult forms of MN are autoimmune diseases without identified etiology (primary MN), linked to the production of antibodies raised against another podocyte antigen, the type-M phospholipase A2 receptor (PLA2R1). Anti-PLA2R1 antibodies are detected in 70 to 80% of patients before any immunosuppressive treatment, and only occasionally in secondary forms of MN, variants of PLAR1 and HLA-DQA1 genes are very significantly associated with occurrence of primary MN in Caucasians. The third mechanism is characterized by immunization against a foreign protein, cationic bovine serum albumin (BSA), which is involved in rare forms of MN during early childhood. This finding points to a possible role of food and environmental antigens in membranous nephropathy.
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PMID:[Pathophysiology of extramembranous glomerulopathies. Fifty years of progress, from laboratory to patient]. 2459 73

Since the early 2000s, considerable advances have been achieved in the understanding of molecular pathomechanisms of human membranous nephropathy (MN), inspired by studies of Heymann nephritis, a faithful experimental model. These studies led to the identification of neutral endopeptidase, the type-M phospholipase A2 receptor (PLA2R), and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in neonatal alloimmune, adult 'idiopathic', and early childhood MN, respectively. A genome-wide association study further showed a highly significant association of the PLA2R1 and the HLA-DQA1 loci with idiopathic MN in patients of white ancestry. The time has come to revisit the spectrum of MN based on the newly identified antigen-antibody systems which should be considered as molecular signatures of the disease, challenging the uniform histological definition. Although some uncertainties remain as to the pathogenic effects of anti-PLA2R antibodies because of the lack of an appropriate experimental model, the value of these antibodies as biomarkers for diagnosis and disease activity is increasingly being recognized. It is not exaggerated to state that they have induced a paradigm shift in the monitoring of patients with MN, thus opening a new era of personalized medicine.
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PMID:Anti-phospholipase A2 receptor antibodies and the pathogenesis of membranous nephropathy. 2540 74