scholarly journals How Times Have Changed! A Cornucopia of Antigens for Membranous Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiffany N. Caza ◽  
Laith F. Al-Rabadi ◽  
Laurence H. Beck
Keyword(s):  
Membranous Nephropathy ◽  
Rapid Identification ◽  
Target Antigen ◽  
The Novel ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor ◽  
Major Target ◽  
Immune Complex Formation

The identification of the major target antigen phospholipase A2 receptor (PLA2R) in the majority of primary (idiopathic) cases of membranous nephropathy (MN) has been followed by the rapid identification of numerous minor antigens that appear to define phenotypically distinct forms of disease. This article serves to review all the known antigens that have been shown to localize to subepithelial deposits in MN, as well as the distinctive characteristics associated with each subtype of MN. We will also shed light on the novel proteomic approaches that have allowed identification of the most recent antigens. The paradigm of an antigen normally expressed on the podocyte cell surface leading to in-situ immune complex formation, complement activation, and subsequent podocyte injury will be discussed and challenged in light of the current repertoire of multiple MN antigens. Since disease phenotypes associated with each individual target antigens can often blur the distinction between primary and secondary disease, we encourage the use of antigen-based classification of membranous nephropathy.

Serum Anti-PLA2R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

2016 ◽  
Vol 43 (2) ◽  
pp. 129-140 ◽  
Author(s):  
Shi-Yao Wei ◽  
Yu-Xiao Wang ◽  
Jian-Si Li ◽  
Shi-Lei Zhao ◽  
Tian-Tian Diao ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Membranous Nephropathy ◽  
Immunosuppressive Agents ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Phospholipase A2 Receptor ◽  
Significant Difference ◽  
Major Target

Background: M-type phospholipase A2 receptor (PLA2R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA2R (gPLA2R) and the associations of serum anti-PLA2R antibody (sPLA2R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. Methods: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA2R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA2R was assessed by immunofluorescence. Results: Most patients with IMN displayed both gPLA2R and sPLA2R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA2R or sPLA2R-Ab positive. The sPLA2R-Ab titre, not gPLA2R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA2R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA2R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA2R intensity and outcome. Conclusions: These data indicate that sPLA2R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA2R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.

A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients

2020 ◽  
Vol 97 (5) ◽  
pp. 913-919 ◽  
Author(s):  
Catherine Meyer-Schwesinger ◽  
Nicola M. Tomas ◽  
Silke Dehde ◽  
Larissa Seifert ◽  
Irm Hermans-Borgmeyer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor

Routine immunohistochemical staining in membranous nephropathy: in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain

2018 ◽  
Vol 31 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Vincenzo L’Imperio ◽  
Federico Pieruzzi ◽  
Renato Alberto Sinico ◽  
Manuela Nebuloni ◽  
Antonio Granata ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Immunohistochemical Staining ◽  
Phospholipase A2 Receptor ◽  
In Situ Detection

scholarly journals M-Type Phospholipase A2 Receptor Staining in Children with Idiopathic Membranous Nephropathy: PLA2R Staining in Children with IMN

2019 ◽  
Vol 12 (1) ◽  
pp. 27-32
Author(s):  
Yosuke Inaguma ◽  
Atsutoshi Shiratori ◽  
Taku Nakagawa ◽  
Kyoko Kanda ◽  
Makiko Yoshida ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Renal Biopsy ◽  
Clinical Data ◽  
Membranous Nephropathy ◽  
Pediatric Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Target Antigen ◽  
Positive Staining ◽  
Phospholipase A2 Receptor

Background: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome in adults that can also occur in children, albeit less frequently. Recently, the M-type phospholipase A2 receptor (PLA2R) was identified as the target antigen in idiopathic membranous nephropathy (IMN), making it a useful marker for diagnosis. However, there are few studies describing the potential role of PLA2R in children with IMN. The aim of this study was to clarify the involvement of PLA2R in childhood IMN. Methods: We enrolled 11 patients diagnosed with IMN from January 1998 to March 2017. We performed PLA2R staining in paraffin-embedded renal biopsy sections. The clinical data were collected from the patients’ medical records. Results: The median age at biopsy was 6 years (range, 4 to 14 years). A single 6-year-old boy among all pediatric patients with IMN had granular PLA2R staining along his glomerular capillary loops and the prevalence of PLA2R-positivity was 9%. He also showed IgG4 co-dominant staining in terms of IgG subclass. There were no apparent differences in his clinical features such as clinical data at the time of renal biopsy, the time from the treatment initiation to remission, and relapse or renal dysfunction during the follow-up period. Conclusion: We suggest that PLA2R staining can be a diagnostic tool for patients with IMN of any age, though pediatric patients with IMN have lower prevalence of PLA2R-positive staining than adult patients.

scholarly journals Wenyang Lishui Decoction Ameliorates Podocyte Injury in Membranous Nephropathy Rat and Cell Models by Regulating p53 and Bcl-2

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huan Lu ◽  
Yuezhong Luo ◽  
Baolin Su ◽  
Shuifu Tang ◽  
Gangyi Chen ◽  
...  
Keyword(s):  
Kidney Function ◽  
Aqueous Extract ◽  
Membranous Nephropathy ◽  
Molecular Mechanisms ◽  
Distilled Water ◽  
Cell Models ◽  
Clinical Trial Registry ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor ◽  
Significant Difference

Wenyang Lishui decoction (WYD) has been frequently used to treat patients with membranous nephropathy (MN) in China. Our previous study in vitro showed that WYD aqueous extract could alleviate F-actin reorganization of podocytes induced by serum from idiopathic membranous nephropathy (IMN) patients. This study aims to investigate the effects and molecular mechanisms of WYD on MN. MN rat models were induced by cationic bovine serum albumin. Experimental rats were divided into four groups: normal, model, WYD, and benazepril. The normal group consisted of normal rats receiving distilled water for four weeks, while the model, WYD, and benazepril groups consisted of MN rats receiving distilled water, 16.5 g/kg/day WYD aqueous extract, and 10 mg/kg/day benazepril, respectively. Alanine aminotransferase, kidney function, albumin, and 24 h urine total protein (UTP) were measured. Hematoxylin-eosin and electron microscopy analyses were performed. Mouse podocytes were induced to develop cell models by serum from IMN patients with antibody to the M-type phospholipase A2 receptor and spleen and kidney Yang deficiency syndrome. They were divided into five groups: control, model, 2 mg/ml WYD, 4 mg/ml WYD, and 8 mg/ml WYD. CCK-8 assays, flow cytometry, qRT-PCR, and Western blot analyses were performed. In the animal experiment, side effects of WYD were not found. Also, there was no significant difference in kidney function among the groups. In addition, UTP level was significantly reduced, and kidney histological damage was restored in both WYD and benazepril groups but difference in UTP level between them was not found. In the cell experiment, apoptosis rate was increased in the model group while it was decreased by coincubation with WYD. Besides, mRNA and protein levels of p53 were decreased, and those of Bcl-2 were increased by treatment using WYD. In conclusion, WYD could reduce proteinuria and ameliorate podocyte injury by regulating the expression of p53 and Bcl-2. The study is registered in the Chinese Clinical Trial Registry (ChiCTR-OCH-14005137).

P0382“FALSE” POSITIVITY OF SERUM ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY (ANTI-PLA2R AB) IN PATIENTS WITH NON MEMBRANOUS GLOMERULAR DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irene Mok ◽  
Jason Choo
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Asian Population ◽  
Southeast Asian ◽  
Glomerular Disease ◽  
Target Antigen ◽  
Specific Marker ◽  
Major Advance ◽  
Phospholipase A2 Receptor ◽  
Antibody Levels

Abstract Background and Aims Phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN) and the detection of circulating autoantibodies to PLA2R (Anti-PLA2R Ab) is a major advance in understanding this disease. In this study, we aimed to determine if Anti-PLA2R Ab serves as a specific marker for PMN in our multi-ethnic Southeast Asian cohort. Method This was a prospective cohort study of all adults with glomerular disease undergoing biopsy between 1st January 2015 and 30th June 2018. Anti-PLA2R antibody levels were quantitatively determined by IgG ELISA (Euroimmun). Results are expressed as RU/ml. We considered a value of >20RU/ml to represent a positive result, value of <14RU/ml to be negative and values between 14-20 RU/ml to be indeterminate. Results Out of the cohort of 192 patients, there were 27 patients with Membranous Nephropathy (MN), with 12 PMN and 15 with secondary MN (SMN). Secondary causes were Hepatitis (1), Malignancy (1), Lupus (13). In our analyses, 10 (83.3%) PMN pts were positive for Anti-PLA2R Ab, with 7(58.3%) strongly positive with titres >200RU/ml and 2(16.7%) negative. For SMN, the majority, 12 out of 14 patients (85.7%) tested negative and the remaining 2 (7.7%) yielded values of indeterminate levels. Of note, among the 165 patients with non membranous glomerular disease, there were 15 patients (9.1%) with indeterminate Anti-PLA2R Ab levels and 31 patients (18.9%) tested positive for Anti-PLA2R antibody, with levels >20 RU/ml. Of these 31 patients, the majority of the patients had low levels of Anti-PLA2R Ab of <50 RU/ml. However there were 5 patients who had considerably high levels of Anti-PLA2R Ab of >50 RU/ml and their characteristics are tabled below (Table 1) Conclusion Consistent with other published studies, positive Anti-PLA2R antibody levels were highly specific for PMN in our multi-ethnic Southeast Asian population and our centre has since been consistently using this test for differentiating between PMN and SMN. What is most striking in our study is that we have found high-titre Anti-PLA2R antibody positivity in non-MN patients, which has not been frequently reported in literature. The unifying feature amongst these patients appear to be the presence of arterial and arteriolar sclerosis which is usually non-specific. Though we would not normally do the Anti-PLA2R antibody test in a patient with low suspicion of MN, our study findings warrants further investigation and may indicate the limited usefulness of Anti-PLA2R antibody levels as a screening tool for glomerulonephritis.

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