Role of anti-phospholipase A2 receptor antibodies in monitoring of the clinical status in idiopathic membranous nephropathy in Egyptian patients

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.

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Anti-Phospholipase A2 Receptor Antibodies as Diagnostic Modality in Primary Idiopathic Membranous Nephropathy

Annals of Pathology and Laboratory Medicine ◽

10.21276/apalm.1891 ◽

2018 ◽

Vol 5 (7) ◽

pp. A591-597

Author(s):

Ashutosh Rath ◽

Sonia Badwal ◽

Rohit Tewari ◽

Prashant Sengupta ◽

Arun Kumar

Keyword(s):

Phospholipase A2 ◽

Membranous Nephropathy ◽

Idiopathic Membranous Nephropathy ◽

Diagnostic Modality ◽

Phospholipase A2 Receptor ◽

Receptor Antibodies

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Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody

Disease Markers ◽

10.1155/2021/9965343 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Hao-yuan Cui ◽

Chao Li ◽

Hang Li ◽

Yu-bing Wen ◽

Lin Duan ◽

...

Keyword(s):

Phospholipase A2 ◽

Membranous Nephropathy ◽

Serum Antibody ◽

Chinese Patients ◽

Idiopathic Membranous Nephropathy ◽

Igg Subclass ◽

Electron Microscopic ◽

Phospholipase A2 Receptor ◽

Stage 1

Background. The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. Methods. Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related ( n = 132 ) and PLA2R-unrelated ( n = 25 ) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. Results. We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass ( P > 0.05 ). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup ( P = 0.044 , P = 0.013 ). PLA2R-related subgroup showed higher IgG4 intensity ( 2.1 ± 0.6 vs. 1.6 ± 0.7 , P = 0.001 ) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015 ) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages ( P > 0.05 ). Conclusions. Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.

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

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2018-0044 ◽

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.

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