scholarly journals Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience

2020 ◽  
Author(s):  
Brunetta Porcelli ◽  
Andrea Guarnieri ◽  
Fabio Ferretti ◽  
Guido Garosi ◽  
Lucia Terzuoli ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Clinical Diagnosis ◽  
Membranous Nephropathy ◽  
Immunosuppressive Treatment ◽  
Positive Likelihood Ratio ◽  
Idiopathic Membranous Nephropathy ◽  
Renal Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Special Focus ◽  
Phospholipase A2 Receptor

Abstract Background Autoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay. Methods The purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment. Results According to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance. Conclusion Depending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.

Anti-Phospholipase A2 Receptor Antibody as Prognostic Indicator in Idiopathic Membranous Nephropathy

2015 ◽  
Vol 42 (3) ◽  
pp. 250-257 ◽  
Author(s):  
Yang Gyun Kim ◽  
Young-Wook Choi ◽  
Se-Yun Kim ◽  
Ju Young Moon ◽  
Chun-Gyoo Ihm ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Remission Rate ◽  
High Titer ◽  
Severe Disease ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Receptor Antibody ◽  
Phospholipase A2 Receptor

Background: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful in diagnosing idiopathic membranous nephropathy (IMN). We investigated the clinical relevance of PLA2R-Ab enzyme-linked immunosorbent assay (ELISA) in patients with IMN. Methods: We measured PLA2R-Ab with an ELISA kit from the serum of 160 patients with IMN (n = 93), secondary MN (n = 14) and other glomerulonephritis (n = 41) as well as healthy controls (n = 12) at the time of renal biopsy and investigated the correlation of titers of PLA2R-Ab with clinical parameters. Results: PLA2R-Ab was positive in 41 of 93 patients (44.1%) with IMN. No samples from the patients with secondary MN and other glomerulonephritis or healthy controls were positive with the ELISA test. The PLA2R-Ab-positive patients showed severe disease activity and a low remission rate. The PLA2R-Ab titer positively correlated with proteinuria and was negatively associated with renal function and serum albumin. The patients with a high titer of PLA2R-Ab had significantly decreased remission rates. The cumulative probabilities of remission was significantly lower in patients with PLA2R-Ab (p = 0.01) and even so in patients with a high titer of PLA2R-Ab (p = 0.04). When we compared the ELISA titers with Western blot (WB) data of 43 patients who had been enrolled in our previous study, 18 and 30 patients were positive on ELISA (41.9%) and WB (69.8%), respectively. WB and ELISA had a concordance rate of 72.1% and were positively correlated (r = 0.590, p < 0.001). Conclusion: The presence, as well as a high titer, of PLA2R-Ab on ELISA was associated with poor prognosis of IMN. Assessment of PLA2R-Ab with ELISA is an easy and reliable tool for the diagnosis and guidance of therapeutic plans.

scholarly journals Circulating anti-phospholipase A2 receptor antibodies as a diagnostic and prognostic marker in Greek patients with idiopathic membranous nephropathy – a retrospective cohort study

2019 ◽  
Vol 57 (2) ◽  
pp. 141-150
Author(s):  
Simella Provatopoulou ◽  
Dimitra Kalavrizioti ◽  
Maria Stangou ◽  
Maria-Nikoleta Kouri ◽  
Pantellitsa Kalliakmani ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Complete Remission ◽  
Phospholipase A2 ◽  
Disease Activity ◽  
Membranous Nephropathy ◽  
Clinical Status ◽  
Immunosuppressive Treatment ◽  
Idiopathic Membranous Nephropathy ◽  
Phospholipase A2 Receptor

Abstract Introduction. Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy. Methods. Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity. Results. Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse. Conclusions. Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.

A novel time-resolved fluoroimmunoassay based on magnetic microspheres method for detecting antibodies against Phospholipase A2 Receptor

2021 ◽  
Author(s):  
ting li ◽  
qingqing wu ◽  
Xue Yang ◽  
Yueming liu ◽  
bo lin ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Disease Activity ◽  
Membranous Nephropathy ◽  
Magnetic Microspheres ◽  
Idiopathic Membranous Nephropathy ◽  
Serum Antibodies ◽  
Time Resolved ◽  
Phospholipase A2 Receptor

Background: The level of serum antibodies against the M-type phospholipase A2 receptor (anti-PLA2R-IgG) is closely related to the disease activity of idiopathic membranous nephropathy (IMN). Therefore, the establishment of a...

scholarly journals Phospholipase A2 Receptor (PLA2R1) Sequence Variants in Idiopathic Membranous Nephropathy

2013 ◽  
Vol 24 (4) ◽  
pp. 677-683 ◽  
Author(s):  
Marieke J.H. Coenen ◽  
Julia M. Hofstra ◽  
Hanna Debiec ◽  
Horia C. Stanescu ◽  
Alan J. Medlar ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Idiopathic Membranous Nephropathy ◽  
Sequence Variants ◽  
Phospholipase A2 Receptor

scholarly journals Diagnostic Utility of Serum and Urine Biomarkers in Idiopathic Membranous Nephropathy: a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Dan Gao ◽  
Li-Ping Lu ◽  
Zhi-Guo Zhao
Keyword(s):  
Clinical Diagnosis ◽  
Membranous Nephropathy ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Idiopathic Membranous Nephropathy ◽  
Circular Rnas ◽  
Type I ◽  
Diagnostic Efficiency ◽  
Phospholipase A2 Receptor ◽  
The Future

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.

scholarly journals Phospholipase A2 Receptor Antibody IgG4 Subclass Improves Sensitivity and Specificity in the Diagnosis of Idiopathic Membranous Nephropathy

2019 ◽  
Vol 44 (4) ◽  
pp. 848-857 ◽  
Author(s):  
Biao Huang ◽  
Yi Zhang ◽  
Liang Wang ◽  
Wenwei Xu ◽  
Jue Zhang ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Sensitivity And Specificity ◽  
Membranous Nephropathy ◽  
Kidney Diseases ◽  
Measurement Range ◽  
Idiopathic Membranous Nephropathy ◽  
Time Resolved ◽  
Specificity And Sensitivity ◽  
Phospholipase A2 Receptor ◽  
Highly Sensitive

Aims: The aim of this study was to develop a new method for detecting anti-phospholipase A2 receptor-IgG4 to improve the sensitivity and specificity in the diagnosis of idiopathic membranous nephropathy (IMN). Methods: A highly sensitive quantitative assay was developed for the detection of serum anti-phospholipase A2 receptor-IgG4 with europium chelation by time-resolved fluoroimmunoassay (TRFIA), and a mouse anti-human IgG4 tracer was prepared using europium chelation for detection. The specificity and sensitivity of anti-phospholipase A2 receptor-IgG4 in the diagnosis of IMN were further assessed in patients with different kidney diseases. Results: The detection limit of anti-PLA2R-IgG4 was 0.69 ng/mL. The measurement range of anti-PLA2R-IgG4 TRFIA was 0.69–2,500 ng/mL. Mean serum anti-PLA2R-IgG4 was 21.27 ± 15.15 ng/mL in 45 healthy volunteers, 31.08 ± 18.17 ng/mL in 29 IgA nephropathy patients, 49.10 ± 34.32 ng/mL in 8 lupus nephropathy patients, and 10,324.11 ± 17,030.40 ng/mL in 30 IMN patients. The anti-PLA2R-IgG4 cutoff concentration was >161.2 ng/mL with the sensitivity of 90.0% and specificity of 100% in the diagnosis of IMN. However, the cutoff for other kidney diseases was lower than 161.2 ng/mL. Conclusion: The serum anti-phospholipase A2 receptor IgG4 detected with the method developed in this study has higher sensitivity and higher specificity than total IgG in the diagnosis of IMN.

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