The pathogenesis of membranous nephropathy

Glassock, Richard J.

doi:10.1097/mnh.0b013e3283522ea8

Cited by 58 publications

(24 citation statements)

References 39 publications

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“…Membranous nephropathy (MN) is another form of immune-mediated glomerular injury in which immune complexes of immunoglobulins and complement accumulate in a granular pattern along the outer side of the GBM, leading to glomerular visceral epithelial cell detachment 90 (see the articles by Beck et al and Takano and Cybulsky). Seminal studies have identified several autologous antigens that are targets of antibody response in MN.…”

Section: Complement In Kidney Diseasesmentioning

confidence: 99%

Overview of Complement Activation and Regulation

Noris

Remuzzi

2013

Seminars in Nephrology

669

633

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SummaryComplement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured cells. In normal conditions complement is tightly controlled by a number of fluid-phase and cell surface proteins to avoid injury to autologous tissues. When complement is hyperactivated, as occurs in autoimmune diseases or in subjects with dysfunctional regulatory proteins, it drives a severe inflammatory response in numerous organs. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury. Injury may derive from deposition of circulating active complement fragments in glomeruli, but complement locally produced and activated in the kidney also may have a role. Many kidney disorders have been linked to abnormal complement activation, including immune-complex–mediated glomerulonephritis and rare genetic kidney diseases, but also tubulointerstitial injury associated with progressive proteinuric diseases or ischemia-reperfusion.

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Section: Complement In Kidney Diseasesmentioning

confidence: 99%

Overview of Complement Activation and Regulation

Noris

Remuzzi

2013

Seminars in Nephrology

669

633

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“…PLA2R is a transmembrane protein located on the surface of human podocytes and colocalizes with IgG4 in the immune deposits of glomeruli in patients with IMN. Binding of the circulating anti-PLA2R antibody to the PLA2R antigen on glomerular podocytes to form an in situ immune complex activates a complement to cause podocyte and immune damage that results in urinary protein production, ultimately causing kidney damage (Glassock, 2012). Additionally, Beck et al found that serum anti-PLA2R antibodies were detectable in 70% of patients with IMN and detected at a low rate in people without kidney disease and other kidney patients (Hofstra & Wetzels, 2014).…”

Section: Introductionmentioning

confidence: 99%

Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody

Guo

Yan

Gao

et al. 2020

PeerJ

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Background To discuss the clinicopathological features and prognosis of patients with idiopathic membranous nephropathy (IMN) who are serum-negative for the anti-PLA2R antibody. Method Overall, 229 IMN patients were retrospectively collected in this study and classified into anti-PLA2R antibody-negative (PLA2R−, 59 cases) and antibody-positive (PLA2R+, 170 cases) groups. The clinical and pathological features of the PLA2R− group were analyzed; 162 patients in both groups were followed up, and the PLA2R antigen was detected in renal biopsies from the PLA2R− group. Kaplan-Meier and survival analyses were used to compare differences in prognosis. Results Serum albumin levels were higher and 24-hour urine protein, creatinine, and beta 2-microglobulin (BMG) levels were lower in the PLA2R− group than in the PLA2R+ group; the proportion of acute and chronic tubular lesions was also significantly lower in the PLA2R− group than in in the PLA2R+ group. After treatment, the remission rate was significantly higher in the negative group than in the positive group (93.02% vs 74.78%,), especially the rate of complete remission (51.16% vs 23.47%). Furthermore, the PLA2R antigen-positive staining rate of 43 patients in the PLA2R− group was 62.79%. Although not significant, the survival rate was higher in the PLA2R− group than in the PLA2R+ group. BMG, 24-hour urine protein and acute and chronic tubular lesions were risk factors for kidney death, and 24-hour urine protein was an independent risk factor for kidney death. Conclusions Compared with the PLA2R+ group, the PLA2R− group had mild clinical manifestations and pathological damage and a higher clinical treatment remission rate. Renal tissue PLA2R antigen testing can be considered for patients with seronegative IMN to increase the diagnostic rate.

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“…IMN is an autoimmune disease caused by endogenous antigens combined with specific antibodies in the circulation to form in situ immune complexes that are deposited in renal tissues. The anti-PLA2R antibody in circulation binds to PLA2R on the surface of podocytes to form an electrondense deposit under the foot process and epithelium, thereby activating the complement-forming membrane attack complex, causing podocyte and kidney damage (Glassock 2012). Several studies have demonstrated that the anti-PLA2R antibody is a key factor in the pathogenesis of IMN.…”

Section: Discussionmentioning

confidence: 99%

“…Binding of the circulating anti-PLA2R antibody to the PLA2R antigen on glomerular podocytes to form an in situ immune complex activates a complement to cause podocyte and immune damage that results in urinary protein production, ultimately causing kidney damage (Glassock 2012). Additionally, Beck et al found that serum anti-PLA2R antibodies were detectable in 70% of patients with IMN and detected at a low rate in people without kidney disease and other kidney patients (Hofstra & Wetzels 2014).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #3 of "Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody (v0.1)"

2020

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Background: To discuss the clinicopathological features and prognosis of patients with idiopathic membranous nephropathy (IMN) who are serum-negative for the anti-PLA2R antibody. Method: Overall, 229 IMN patients were retrospectively collected in this study and classified into anti-PLA2R antibody-negative (PLA2R-, 59 cases) and antibody-positive (PLA2R+, 170 cases) groups. The clinical and pathological features of the PLA2R-group were analyzed; 162 patients in both groups were followed up, and the PLA2R antigen was detected in renal biopsies from the PLA2R-group. Kaplan-Meier and survival analyses were used to compare differences in prognosis. Results: Serum albumin levels were higher and 24-hour urine protein, creatinine, and beta 2microglobulin (BMG) levels were lower in the PLA2R-group than in the PLA2R+ group; the proportion of acute and chronic tubular lesions was also significantly lower in the PLA2R-group than in in the PLA2R+ group. After treatment, the remission rate was significantly higher in the negative group than in the positive group (93.02% vs 74.78%,), especially the rate of complete remission (51.16% vs 23.47%). Furthermore, the PLA2R antigen-positive staining rate of 43 patients in the PLA2R-group was 62.79%. Although not significant, the survival rate was higher in the PLA2R-group than in the PLA2R+ group. BMG, 24-hour urine protein and acute and chronic tubular lesions were risk factors for kidney death, and 24-hour urine protein was an independent risk factor for kidney death. Conclusions: Compared with the PLA2R+ group, the PLA2R-group had mild clinical manifestations and pathological damage and a higher clinical treatment remission rate. Renal tissue PLA2R antigen testing can be considered for patients with seronegative IMN to increase the diagnostic rate.

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The pathogenesis of membranous nephropathy

Abstract: The identification of target antigens provides new tools for diagnosis, prognosis and monitoring of therapy in human membranous nephropathy.

Cited by 58 publications

References 39 publications

Overview of Complement Activation and Regulation

Overview of Complement Activation and Regulation

Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody

Peer Review #3 of "Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody (v0.1)"

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