phospholipase a2 receptor
Recently Published Documents


TOTAL DOCUMENTS

343
(FIVE YEARS 161)

H-INDEX

32
(FIVE YEARS 7)

2022 ◽  
Vol 12 ◽  
Author(s):  
Le Deng ◽  
Qipeng Huang ◽  
Jiang Wang ◽  
Kaiping Luo ◽  
Jiarong Liu ◽  
...  

Background: This study aimed to evaluate clinical features and prognosis and therapy option of patients with different risk ranks based on antibody against the M-type phospholipase-A2-receptor (PLA2Rab) level in seropositive M-type phospholipase-A2-receptor (PLA2R)-associated membranous nephropathy (MN) in a large sample size, multi-center study.Method: Based on the unvalidated cut-off value of PLA2Rab above 150 RU/ml as one of the clinical criteria for high risk of progressive kidney function loss in MN according to 2020 Kidney Disease: Improving Global Outcomes (KDIGO) draft guidelines recommendation, a total of 447 patients who received cyclophosphamide (CTX) or tacrolimus (TAC) combined with corticosteroids treatment for 12 months were divided into high titer (>150 RU/ml) group and non-high titer (20–150 RU/ml) group, which were subdivided into CTX subgroup and TAC subgroup. The overall cohort was classified into CTX group and TAC group as well. Clinical parameters levels and remission rates were recorded at 3, 6, and 12 months follow-up. PLA2Rab was tested by enzyme-linked immunosorbent assay.Results: Patients with high titer PLA2Rab were associated with more severe proteinuria and hypoalbuminemia compared to those with non-high titer antibody, accompanied by lower complete remission (CR) and total remission (TR) rates at 3, 6, and 12 months, which even took longer to remission. Similar remission rates differences between the two titer groups were observed in the CTX and TAC groups, respectively. PLA2Rab level at baseline was an independent predictive factor for CR and TR. In the high titer group, CR and TR rates in the CTX subgroup were significantly higher than those in the TAC subgroup at 12 months, although serious adverse events were more frequent in the former.Conclusion: High-risk rank patients with PLA2Rab level above 150 RU/ml have higher disease activity and worse prognosis among patients with seropositive PLA2R-associated MN, even under different immunosuppressive therapeutic models; moreover, CTX combined with corticosteroids was preferred compared to TAC plus corticosteroids, although serious adverse events were more frequent in the former. Additionally, baseline PLA2Rab level was an independent predictive factor for clinical remission.


Nephron ◽  
2021 ◽  
pp. 1-4
Author(s):  
Emel Isiktas Sayilar ◽  
Saba Kiremitci ◽  
Ihsan Ergun ◽  
Arzu Ensari

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and >70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient.


Author(s):  
Tala Pourlak ◽  
Sonya Sharifi ◽  
Sepideh Zununi Vahed ◽  
Elham Ahmadian ◽  
Magali Cucchiarini

Abstract Membranous glomerulonephritis (MGN) is the most common cause of adulthood nephrotic syndrome. Diagnosis of membranous nephritis is based on light electron immunofluorescence microscopy and clinical signs. Immune complex deposition against podocyte antigens such as phospholipase A2 receptor (PLA2R) activates the complement system. Of this, complement Component C4d (C4d) is involved in the classical and lectin pathways. This marker may be used by immunohistochemistry to diagnose MGN when other methods are not available. In this work, C4d expression was monitored by immunohistochemical analysis in the glomerular capillaries of patients with primary MGN (study group, N=33) versus patients with minimal change disease (MCD, control group, N=20) in a cross-sectional evaluation performed based on the diagnosis confirmed by light microscopy and immunofluorescence. There was no significant demographic difference between the two groups except for age (P=0.002). C4d immune-expression was positive in glomerular capillary (2+ to 4+) in most of the MGN patients, while it was negative in the MCD group. The sensitivity and specificity of C4d immunostaining were 95% and 100%, respectively. The Pearson correlation coefficient was 0.74 between C4d (immunohistochemistry) and immunoglobulins (IgG; immunofluorescence) and 0.65 between C4d (immunohistochemistry) and the C3 complement product (immunofluorescence). Immunohistochemical evaluation of C4d is, therefore, a sensitive and specific method that has a high correlation with IgG immunofluorescence.


2021 ◽  
Author(s):  
Dan Gao ◽  
Li-Ping Lu ◽  
Zhi-Guo Zhao

Abstract Background Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific biomarkers for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, there are limited data about their diagnostic value. Therefore, an overall meta-analysis helps to identify effective biomarkers for the clinical diagnosis of IMN. Methods A systematic literature search was carried out in PubMed, Embase, Cochrane and Web of Science from inception until December 31, 2020. Two researchers searched for studies that met the inclusion criteria. The results of the joint study were expressed in terms of sensitivity and specificity. Results The meta-analysis included 24 studies with biomarkers for the clinical diagnosis of IMN, including phospholipase A2 receptor (PLA2R), thrombospondin type I domain-containing 7A (THSD7A), lysosome membrane protein-2 (LIMP-2) and circular RNAs. The diagnostic efficiency of PLA2R for IMN had a combined sensitivity of 60% and a combined specificity of 100%. The diagnostic efficiency of THSD7A for IMN had a combined sensitivity of 3% and a combined specificity of 99%. The diagnostic efficiency of urinary LIMP-2 for IMN was 100%, and the specificity was 100%. The diagnostic efficiency of exosomal circRNAs for IMN was 100%, and the specificity was 100%. Conclusions This meta-analysis shows that PLA2R and THSD7A are of important diagnostic value for IMN. More studies are needed in the future to reveal the diagnostic value of LIMP-2 and circRNAs for IMN. At the same time, other new diagnostic biomarkers in IMN need to be found in the future.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tiffany N. Caza ◽  
Laith F. Al-Rabadi ◽  
Laurence H. Beck

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.


Nephron ◽  
2021 ◽  
pp. 1-5
Author(s):  
Gabriel Giannini ◽  
Lois J. Arend

<b><i>Introduction:</i></b> Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. <b><i>Methods:</i></b> A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. <b><i>Results:</i></b> Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. <b><i>Conclusion:</i></b> PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.


2021 ◽  
pp. 334-339
Author(s):  
Lyle W. Baker ◽  
Jaime Jimenez-Lopez ◽  
Xochiquetzal J. Geiger ◽  
Nabeel Aslam

Membranous nephropathy (MN) is currently classified as either primary – often associated with positive anti-phospholipase-A2 receptor (PLA2R) autoantibodies – or as secondary – associated with malignancy, infection, medications, or autoimmune disease. We present a case of biopsy-proven MN with very high serum titer of anti-PLA2R autoantibodies in a patient with a synchronous diagnosis of poorly differentiated esophageal adenocarcinoma and renal cell carcinoma who presented with nephrotic syndrome. Based on the current classification, MN in the presence of active malignancy is diagnosed as secondary and unlikely to have positive anti-PLA2R autoantibodies. This raises several questions: whether this patient has secondary MN associated with malignancy and coincidentally discovered anti-PLA2R autoantibodies, primary MN due to anti-PLA2R autoantibodies with coincidentally discovered malignancy, or whether malignancy can induce the formation of anti-PLA2R autoantibodies that result in MN. This case report highlights the importance of age-appropriate cancer screening, even in patients with presumed primary MN and positive anti-PLA2R autoantibodies.


Author(s):  
Shane A. Bobart ◽  
Heedeok Han ◽  
Shahrzad Tehranian ◽  
An S. De Vriese ◽  
Juan Carlos Leon Roman ◽  
...  

Background and objectivesKidney biopsy is the current gold standard to diagnose membranous nephropathy. Approximately 70%–80% of patients with primary membranous nephropathy have circulating anti-phospholipase A2 receptor antibodies. We previously demonstrated that in proteinuric patients with preserved eGFR and absence of associated conditions (e.g., autoimmunity, malignancy, infection, drugs, and paraproteinemia), a positive anti-phospholipase A2 receptor antibody test by ELISA and immunofluorescence assay confirms the diagnosis of membranous nephropathy noninvasively. These data have not been externally validated.Design, setting, participants, & measurementsThe clinical and pathologic characteristics of patients with a positive anti-phospholipase A2 receptor antibody test at the Mayo Clinic, the University Hospital Vall D’Hebron (Barcelona), and the Columbia University Medical Center (New York) were retrospectively reviewed. Biopsy findings and presence or absence of a potential associated condition were assessed.ResultsFrom a total of 276 patients with positive anti-phospholipase A2 receptor serology, previously reported patients (n=33), kidney transplant recipients (n=9), pediatric patients (n=2), and patients without kidney biopsy (n=69) were excluded. Among the 163 remaining patients, associated conditions were identified in 47 patients, and 15 patients had diabetes mellitus. All 101 patients of the final cohort had a primary diagnosis of membranous nephropathy on kidney biopsy. In the 79 patients with eGFR≥60 ml/min per 1.73 m2, none of the biopsy findings altered diagnosis or management. Among the 22 patients with decreased eGFR, additional findings included superimposed acute interstitial nephritis (n=1).ConclusionsIn patients with preserved eGFR and absence of associated conditions or diabetes, a positive anti-phospholipase A2 receptor test by either ELISA >20 RU/ml or a positive immunofluorescence assay confirms the diagnosis of membranous nephropathy, precluding the requirement for a kidney biopsy.


2021 ◽  
Author(s):  
Hajime Kaga ◽  
Hirotoshi Matsumura ◽  
Takehiro Suzuki ◽  
Naoshi Dohmae ◽  
Masafumi Odaka ◽  
...  

Abstract The aim of this study was to characterize glomerular proteins in primary membranous nephropathy (pMN) and drug-induced secondary MN (sMN) by laser microdissection and comparative proteomic analysis. We used renal biopsy specimens from 6 patients with anti-phospholipase A2 receptor autoantibody (PLA2R Ab) (+) pMN, 6 patients with PLA2R Ab (‒) pMN, 6 patients with bucillamine (BCL)-induced sMN, and 5 control cases (time 0 transplant biopsies). Proteins were extracted from laser-microdissected glomeruli and analyzed using mass spectrometry. The quantification values of protein abundance in each MN group were compared with those in the control group. More than 800 proteins with high confidence were identified. Principal component analysis revealed a different distribution between the pMN and sMN groups. For further analysis, 441 proteins matched with ≥3 peptides were selected. Among the pMN and sMN groups, we compared the profiles of several protein groups based on the structural and functional characteristics, such as immunoglobulins, complements, complement-regulating proteins, podocyte-associated proteins, glomerular basement membrane proteins, and several proteins that are known to be associated with kidney diseases, including MN. Between the pMN and BCL-induced sMN groups, we observed common and different alterations in protein levels such as known disease-associated proteins and potential disease marker proteins.


Sign in / Sign up

Export Citation Format

Share Document