Coexistence of Different Circulating Anti-Podocyte Antibodies in Membranous Nephropathy (original) (raw)
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Podocyte Antigens and Glomerular Disease
Nephron Experimental Nephrology, 2007
Background: Membranous nephropathy (MN), a major cause of nephrotic syndrome in the adult, is an immune-mediated disease characterized by the accumulation of subepithelial immune deposits leading to complement activation and podocyte injury. However, the target antigens of circulating antibodies are unknown. Current treatments for patients with MN are entirely empirical, and concept-driven therapies are dramatically lacking. Methods: Specificity of circulating antibodies and composition of glomerular deposits were analyzed in Heymann nephritis (HN), a faithful rat model of MN, and in a subset of patients with antenatal MN. Results: 20 years after the identification of megalin as the podocyte target antigen of nephritogenic antibodies in HN, we identified the human counterpart of megalin, the enzymatic podocyte antigen neutral endopeptidase (NEP). Antibodies to megalin or NEP induce formation of subepithelial immune deposits and of C5b-9, the membrane attack complex of complement. Co...
Nephron Extra
Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1), n = 20 and IgAN group (G2), n = 39, subdivided into M1E0S0T0 (G2A), n = 21 and M1E0S1T0 (G2B), n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr) and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C) ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hyperten
Podocytopenia and disease severity in IgA nephropathy
Kidney International, 2002
Podocytopenia and disease severity in IgA nephropathy. IgA nephropathy is the most common form of primary Background. IgA nephropathy is a common form of proglomerular nephritis in children and young adults worldgressive glomerular disease, associated with proliferation of wide. Although variable clinically, the disease is characmesangial cells and mesangial deposition of IgA. The present terized by mesangial deposits of IgA associated with study was designed to investigate functional and morphological mesangial cell proliferation, hematuria that is often intercovariates of disease severity in patients with IgA nephropathy. Methods. Glomerular hemodynamics, permselectivity and mittent, and proteinuria that is usually mild. An often ultrastructure were studied in 17 adult patients with IgA neinsidious progression to end-stage renal failure in 25 to phropathy using inulin, para-aminohippuric acid (PAH) and 40% of cases is accompanied by the development of 3 H-Ficoll clearances and morphometric methods. A mathematglomerular sclerosis [1]. D'Amico has proposed funcical model of macromolecule permeation through a heteroportional and structural predictors for the development of ous membrane was used to characterize glomerular permselectivity. Controls consisted of 14 healthy living kidney donors end-stage renal failure based on his analysis of several and 12 healthy volunteers. studies using Kaplan-Meier survival curve methodology Results. The patients were heterogeneous in their disease [2]. These predictors include azotemia, heavy proteinuria severity, but as a group had a decreased glomerular filtration and hypertension at the time of diagnosis, along with rate (GFR) and increased urinary protein excretion compared tubulointerstitial damage and glomerular sclerosis on the to controls [63 Ϯ 29 SD vs. 104 Ϯ 23 mL/min/1.73 m 2 , P Ͻ 0.001, diagnostic biopsy. Other studies also have shown heavy and (median) 1.34 vs. 0.11 g/day, P Ͻ 0.0001, respectively). A multivariate analysis of structural and functional relationships
International Journal of Clinical Practice, 2020
Background Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in nondiabetic adults. M-type phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A) are known as target podocyte antigens in membranous nephropathy (MN). Antibodies against these podocyte antigens are used in the initiation of treatment and response monitoring. However, the relationship between renal podocyte antigens and treatment response is not clear yet. We evaluated the relationship between immunohistochemical PLA2R, THSD7A, and IgG4 staining, clinical findings, and treatment response in kidney biopsies. Methods Fifty-eight patients with MN were included in this retrospective study. In the renal biopsy samples of the patients, PLA2R, THSD7A, and IgG4 were stained immunohistochemically and evaluated by light microscopy. The clinical, laboratory, and treatment results of the patients were obtained from the hospital records.
Membranous Nephropathy Associated With IgG4-Related Disease
American Journal of Kidney Diseases, 2011
Immunoglobulin G4 (IgG4)-related systemic disease is a rare condition characterized by high levels of circulating IgG4 and IgG4-positive plasma cell infiltrates in various organs, including the pancreas, salivary glands, biliary tract, liver, lung, and kidney. We describe a case of a 54-year-old man with IgG4-related systemic disease presenting with autoimmune pancreatitis and Mikulicz disease. Steroid therapy decreased circulating IgG4 levels and promoted regression of clinical signs. Thereafter, an increase in serum IgG4 values was followed by the occurrence of nephrotic-range proteinuria. Kidney biopsy showed membranous nephropathy with no IgG4-positive cell infiltrates. A search for circulating immune complexes was negative, and antibodies against M-type phospholipase A 2 receptor could not be detected. Western blot analyses identified circulating IgG3 reacting with superoxide dismutase 2. This case suggests that membranous nephropathy represents an additional renal manifestation of IgG4-related systemic disease, with a pathogenesis possibly associated with neoproduction of autoantibodies targeting podocyte antigen(s). Am J Kidney Dis. 58 :272-275.
American Journal of Kidney Diseases, 2013
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Idiopathic membranous nephropathy and anti-phospholipase A2 receptor antibodies
Journal of nephropathology, 2013
Idiopathic membranous nephropathy anti-phospholipase A2 receptor antibodies nephrotic syndrome End-stage renal disease Implication for health policy/practice/research/medical education: Membranous nephropathy (MN) is a glomerular disease due to subepithelial immune deposits and local complement activation resulting in podocyte injury and proteinuria. Patients with idiopathic (but not secondary) MN had circulating autoantibodies, predominantly of the IgG4 subclass, directed against M-type phospholipase A2 receptor (PLA2R) located on podocytes. It is also possible that the binding of anti-PLA2R antibodies to PLA2R on podocytes could alter receptor function resulting in podocyte dysfunction.