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

The distribution of a group of glomerular antigens and the composition of deposits was examined by immunoelectron microscopy in patients with idiopathic membranous nephropathy (MN), focal segmental glomerulosclerosis (FSG) and membranoproliferative glomerulonephritis (MPGN). The decrease in expression of common acute lymphoblastic leukemia antigen (CALLA) on glomerular visceral epithelial cells was found in MN and FSG. The loss of CALLA on visceral epithelial cells was typical for immature glomerulus and for this cell culture. On the strength of these results we can suppose that the dedifferentiation of visceral epithelial cells takes place in MN and FSG. It leads to changes in the synthesis of the glomerular basement membrane components.
 ...
PMID:Common acute lymphoblastic leukemia antigen expression on visceral epithelial cells in several types of glomerulonephritis. 830 14

Membranous glomerulonephritis (MGN) is a major cause of the nephrotic syndrome and chronic renal insufficiency. Studies on the reactivity of nephritogenic antibodies implicated in a case of antenatal MGN led to identify for the first time a target of the immune conflict in glomeruli, neutral endopeptidase (CD10). This enzyme that is restricted to certain tissues, being strongly expressed in the placenta and on glomerular podocytes, is involved in the catabolism of a number of regulatory peptides, particularly those involved in vasomotricity. We showed that the nephritogenic antibodies blocked enzymatic activity and that the mother became immunized at the time of a previous pregnancy because she was neutral endopeptidase-deficient. Two additional families have been identified since then. The pathophysiologic mechanisms that we have unraveled are reminiscent of Rhesus immunization and open up new avenues for therapeutic intervention.
 ...
PMID:[Extra-membranous glomerulonephritis: report of a family and new physiopathological concepts]. 1497 57

Membranous nephropathy (MN), the most common cause of idiopathic nephrotic syndrome in white adults, is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. In Heymann nephritis, the rat experimental model for MN, megalin--the target antigen of the nephritogenic antibodies--is expressed on the surface of podocytes, where immune complexes are formed, leading to complement activation and nephrotic-range proteinuria. However, megalin cannot be held responsible for human MN because it has not been found in human podocytes or detected in subepithelial immune deposits in patients with MN. Several potential antigens have been identified in so-called secondary forms of MN, but there is no real proof that these antigens are pathogenic. In a subgroup of infants with antenatal MN, neutral endopeptidase (NEP) has been identified as the first protein target on human podocytes of nephritogenic antibodies. The infants' mothers became immunized during pregnancy against NEP expressed on syncytiotrophoblastic cells because they were NEP deficient as a result of truncating mutations in the MME gene. Severity of neonatal renal disease was determined by the mothers' IgG response that led to the formation of the membrane attack complex of complement in the subepithelial deposits. Alloimmunization against NEP is a novel pathomechanism of MN that might also account for some cases of MN after renal or bone marrow transplantation. Other types of alloimmunization should be investigated in MN but also in other renal and nonrenal diseases, particularly those that affect the pediatric age.
 ...
PMID:Molecular pathomechanisms of membranous nephropathy: from Heymann nephritis to alloimmunization. 1580 Jan 20

The passive trapping of preformed immune complexes is responsible for some forms of glomerulonephritis that are associated with mesangial or subendothelial deposits. The biochemical characteristics of circulating antigens play important roles in determining the biologic activity of immune complexes in these cases. Examples of circulating immune complex diseases include the classic acute and chronic serum sickness models in rabbits, and human lupus nephritis. Immune deposits also form "in situ". In situ immune deposit formation may occur at subepithelial, subendothelial, and mesangial sites. In situ immune-complex formation has been most frequently studied in the Heymann nephritis models of membranous nephropathy with subepithelial immune deposits. While the autoantigenic target in Heymann nephritis has been identified as megalin, the pathogenic antigenic target in human membranous nephropathy had been unknown until the recent identification of neutral endopeptidase as one target. It is likely that there is no universal antigen in human membranous nephropathy. Immune complexes can damage glomerular structures by attracting circulating inflammatory cells or activating resident glomerular cells to release vasoactive substances, cytokines, and activators of coagulation. However, the principal mediator of immune complex-mediated glomerular injury is the complement system, especially C5b-9 membrane attack complex formation. C5b-9 inserts in sublytic quantities into the membranes of glomerular cells, where it produces cell activation, converting normal cells into resident inflammatory effector cells that cause injury. Excessive activation of the complement system is normally prevented by a series of circulating and cell-bound complement regulatory proteins. Genetic deficiencies or mutations of these proteins can lead to the spontaneous development of glomerular disease. The identification of specific antigens in human disease may lead to the development of fundamental therapies. Particularly promising future therapeutic approaches include selective immunosuppression and interference in complement activation and C5b-9-mediated cell injury.
 ...
PMID:Mechanisms of immune-deposit formation and the mediation of immune renal injury. 1618 25

Recent results indicate that intrinsic glomerular cells (podocytes, mesangial and endothelial cells) are active participants in the inflammatory process in the glomerulus. Particular attention is drawn to podocyte injury in glomerulonephritis. Podocytes are end-differentiated cells which have lost their proliferation abilities and can only compensate by hypertrophy. The inability to proliferate is the cost which a podocyte must pay for the development of highly specialized structures and ability to adhere to the glomerular basement membrane. Collapsing focal-segmental glomerulosclerosis is a condition in which podocytes proliferate, but this process is associated with loss of their maturity markers as well as with abnormalities in the expressions of cell cycle proteins. Dysfunction of slit diaphragms is an important element in the pathogenesis of glomerulopathies with marked proteinuria. Recent studies also underline the importance of neprilysin in the pathogenesis of glomerulonephritis. This is the first podocytic antigen which has been shown to induce human membranous glomerulonephritis.
 ...
PMID:[The role of podocytes in normal glomerular function and in the pathogenesis of glomerulonephritis. Part II. Phenotypic and functional changes of podocytes in glomerulonephritis]. 1670 25

Graft rejection has long been considered the paradigm of renal diseases induced by alloimmunization, particularly alloimmunization directed against HLA antigens. Accumulating evidence indicates that non-HLA immunity also has an important role in clinical transplantation. Targets of alloimmunization include antigens of tubular basement membrane, tubular epithelial cells and endothelial cells. They can be polymorphic allovariants (as shown in the rat) or 'hidden' antigens exposed when the graft is damaged. Alloimmunization can also occur when a person genetically deficient in a renal protein (e.g. the alpha5 (IV) collagen chain in X-linked Alport's syndrome or nephrin in Finnish-type nephrotic syndrome) is transplanted to treat end-stage renal failure. The non-mutated protein in the donor kidney is recognized as a foreign antigen, and the resulting alloimmune response can damage the graft. We have demonstrated that alloimmunity can also affect the native kidney. We have characterized a novel fetomaternal disease in which a genetic defect in the MME gene encoding neutral endopeptidase (NEP) in the mother leads to the development of membranous nephropathy in her fetus (maternal anti-NEP antibodies bind to NEP on fetal podocytes). Our findings raise the possibility that mutations or genetic polyporphisms in MME or other genes expressed by the podocyte are involved in alloimmune-mediated development of membranous nephropathy after kidney or bone marrow transplantation.
 ...
PMID:Mechanisms of disease: Alloimmunization in renal diseases. 1693 67

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 white adults. In the rat model of Heymann nephritis, the target antigen of antibodies is megalin, a multiligand receptor expressed at the podocyte cell surface. This review summarizes key findings provided by this experimental model and by our discovery of neutral endopeptidase being the alloantigen involved in neonatal cases of membranous nephropathy. We discuss the role of alloimmunization as a new mechanism of renal disease and the approach that we use to identify new podocyte antigens. We also summarize current knowledge on the mechanism of proteinuria, with special emphasis on the role of complement. In conclusion, substantial progresses have been made in understanding molecular mechanisms of membranous nephropathy, which should lead to novel therapeutic approaches.
 ...
PMID:Target antigens and nephritogenic antibodies in membranous nephropathy: of rats and men. 1789 86

Membranous nephropathy (MN) is one of the most common glomerulopathies. Current treatments are entirely empirical, and concept-driven therapies are dramatically lacking. In the rat experimental model established by Heymann in 1959, the target antigen is expressed at the surface of podocytes where immune complexes are formed, inducing complement activation results in heavy proteinuria. However, megalin is not detected on human podocytes and in immune deposits in patients with MN. We recently identified neutral endopeptidase (NEP), a podocyte antigen that can digest biologically active peptides, as the target antigen of antibodies deposited in the subepithelial space of glomeruli in a subset of patients with antenatal MN. The mothers became immunized because they are deficient in NEP due to truncating mutations in the gene. MN could be transferred to the rabbit by injection of mothers' Ig. We discuss new pathophysiological aspects of the disease with special emphasis on allo-immunization, novel potential antigenic targets, and therapeutic prospects.
 ...
PMID:[Extra-membranous glomerulonephritis: from the experimental model to the human pathology of new-born and adult]. 1902 6

Fetomaternal alloimmunization with antenatal glomerulopathies (FMAIG) is a recently described alloimmune disorder, which results from the production of maternal antibodies that cross the placenta, bind to fetal glomerular podocytes, and mediate renal disease. The pathogenic antibodies are directed against CD10/neutral endopeptidase (NEP). The infant's mother is NEP-deficient and thus she becomes immunized during the first pregnancy against CD10/NEP expressed by placental cells. Because future pregnancies in CD10/NEP-immunized mothers are at high risk for the fetus, detection of anti-NEP antibodies in pregnant mothers and antigen-driven therapies including induction of tolerance, are urgently needed. This ideally requires identification of the pathogenic epitopes born by the antigen and specifically recognized by B- and T-cells. We have recently characterized such epitopes that will be used in diagnostic tests (ELISA) and for new therapeutic approaches based on peptide-specific immune intervention. For this purpose, we have developed an experimental model by crossing NEP/CD10-deficient female mice to wild-type males. The females develop an alloimmune reaction against NEP, which is a prerequisite for tolerance induction experiments. Although NEP/CD10 does not seem to be involved in common idiopathic forms of membranous nephropathy in the adult, alloimmune antibodies may be implicated in de novo membranous nephropathy that develop in the kidney graft and after alloimmune bone marrow transplantation.
 ...
PMID:[Anti-CD10 fetomaternal alloimmunisation]. 1915 96

Neprilysin (NEP, CD10, CALLA-common acute lymphoblastic leukaemia antigen, neutral endopeptidase, enkephalinase) is a zinc-dependent metallopeptidase, which is the first podocytic antigen, which has been shown to induce human membranous glomerulonephritis (GN). Debiec et al. in a case of antenatal membranous GN identified NEP as the podocyte target antigen of circulating antibodies produced by the mother who failed to express NEP on granulocytes. However, NEP is expressed on normal podocytes and renal proximal tubular epithelial cells. Moreover, decreased podocyte expression of NEP has been found in a variety of glomerular diseases. Recent studies show that in patients with GN the podocyte expression of NEP correlates with that of other podocyte proteins, i.e.: synaptopodin and CR1 and reflects the severity of glomerular damage.
 ...
PMID:[The involvement of neprilysin in the pathogenesis of glomerulopathies]. 1982 39


1 2 3 Next >>