Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Katsumata, Yasuhiro; Okamoto, Yuko; Moriyama, Takahito; Moriyama, Rina; Kawamoto, Manabu; Hanaoka, Masanori; Uchida, Keiko; Nitta, Kosaku; Harigai, Masayoshi

doi:10.1080/25785826.2019.1710079

Cited by 9 publications

(13 citation statements)

References 22 publications

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“…Serum albumin and urinary protein are generally used to quantitatively evaluate the severity of nephrotic syndrome in MN, which are important indicators for assessing disease activity ( Kanigicherla et al, 2013 ; Lin et al, 2015 ; Gopalakrishnan et al, 2016 ; Li et al, 2016 ). Consistent with data from aforementioned studies ( Li et al, 2016 ; Song et al, 2018 ; Provatopoulou et al, 2019 ; Katsumata et al, 2020 ; Li et al, 2021 ), we found a significant association of PLA2Rab with urinary protein and serum albumin indicating the correlation between antibody levels and disease activity ( Mahmud et al, 2019 ; Gong et al, 2020 ; Guo et al, 2020 ). However, Jullien et al (2017 ) claimed that the initial PLA2Rab level did not relate to the degree of proteinuria.…”

Section: Discussionsupporting

confidence: 91%

Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer

Deng

Huang

Wang³

et al. 2022

Front. Pharmacol.

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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.

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Section: Discussionsupporting

confidence: 91%

Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer

Deng

Huang

Wang³

et al. 2022

Front. Pharmacol.

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“…For example, only 24-hour urinary protein positively correlated with anti-PLA2R, while albumin, serum creatinine and CysC did not correlate in the study by Li et al [ 19 ]. In two Japanese studies, anti-PLA2R negatively correlated with albumin, but its correlations with serum creatinine and 24-hour urinary protein differed between the two studies [ 21 , 22 ]. The study by Hofstra et al [ 17 ] was consistent with our research on these correlations.…”

Section: Discussionmentioning

confidence: 99%

“…Although Greece also belongs to Europe, the sensitivity in a Greek population was only 48.48% [ 16 ]. In two studies of the Japanese population, the sensitivities were similar, 50.00% and 52.17%, and the specificities were both 100.00% [ 21 , 22 ]. China held four studies, with sensitivities of 62.20%, 60.17%, 50.88%, and 67.26%, and the specificities were all more than 90% [ 19 , 23 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

The optimal anti-phospholipase A2 receptor cutoff for the diagnosis of idiopathic membranous nephropathy: a single-center retrospective study

Guo

et al. 2022

Korean J Intern Med

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Background/Aims Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters. Methods A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency. Results The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate. Conclusions The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

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“…To clarify this important issue and in order to harmonize anti-PLA2R antibody results (thereby correctly assessing anti-PLA2R antibody prevalence in iMN), we reviewed several studies reporting the diagnostic accuracy of anti-PLA2R antibodies using the same ELISA (the only one commercially available), with a cut-off of 20 RU/ml, or 14 RU/ml, or 2.00 and 2.7 RU/ml. At 20 RU/ml, the average sensitivity was 65.5% with 98.4% specificity [12,17,20,21,24,25]. At a cut-off value of 14 RU/ ml, average sensitivity and specificity were 69.1% and 95.2%, respectively [12,20,26,27].…”

Section: Discussionmentioning

confidence: 94%

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

et al. 2020

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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.

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Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Abstract: 2020) Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods, Immunological Medicine, 43:1, 47-56,

Cited by 9 publications

References 22 publications

Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer

Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer

The optimal anti-phospholipase A2 receptor cutoff for the diagnosis of idiopathic membranous nephropathy: a single-center retrospective study

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

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