Comparison of measurements of anti-PLA2R antibodies in Japanese patients with membranous nephropathy using in-house and commercial ELISA

Kaga, Hajime; Komatsuda, Atsushi; Yamamoto, Soh; Kimura, Tadashi; Kamata, Mika; Satô, Akiko; Odaka, Masafumi; Yokota, Shinichi; Takahashi, Naoto; Wakui, Hideki

doi:10.1007/s10157-019-01712-x

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…The mechanisms of MN with solitary polyclonal IgA deposition in the previously reported case and the present case are unknown. In the present case, circulating IgA-class anti-PLA2R antibodies were not detected by our in-house ELISA [7]. Other known autoantigens in patients with primary MN [1] or exogenous mucosal antigens, such as bacterial antigens, may be associated with solitary polyclonal IgA deposition with MN features.…”

Section: Discussionmentioning

confidence: 58%

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Membranous nephropathy with solitary polyclonal IgA deposition: A case report and literature review

Sawamura

Komatsuda

Kaga

et al. 2019

CNCS

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A 60-year-old man presented with nephrotic syndrome (NS). Light microscopy of renal biopsy specimens showed minor glomerular abnormalities, while immunofluorescence microscopy revealed solitary polyclonal granular IgA deposition along the glomerular capillary walls. Electron microscopy showed small amounts of electron-dense deposits in the subepithelial area, but not in the mesangial area. In this patient, apparent underlying disease was not found during the 3-year follow-up, and low-dose prednisolone was effective in the treatment of NS. To our knowledge, there is only one case report of membranous nephropathy with clinicopathological features similar to our case.

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Section: Discussionmentioning

confidence: 58%

“…Monoclonal proteins were not detected in the serum or urine. Circulating IgA-class anti-PLA2R antibodies were not determined by our in-house ELISA [7] using peroxidase-conjugated anti-human IgA as a secondary antibody.…”

Section: Case Reportmentioning

confidence: 99%

Membranous nephropathy with solitary polyclonal IgA deposition: A case report and literature review

Sawamura

Komatsuda

Kaga

et al. 2019

CNCS

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“…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]. Finally, in the studies in which the authors, based on ROC curves, opted for much lower cutoffs (between 2.0 and 2.7 RU/ml), the average sensitivity was 81.8% and the specificity was 93.8% [20-22, 28, 29].…”

Section: Discussionmentioning

confidence: 97%

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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“…The estimated glomerular ltration rate was calculated using the formula for Japanese patients 24 . Circulating PLA2R Abs were measured in pMN patients using enzyme-linked immunosorbent assay (ELISA), in-house ELISA, and a standardized commercial ELISA (Euroimmun, Lübeck, Germany), as described previously 25 .…”

Section: Methodsmentioning

confidence: 99%

Proteomic Analysis of Glomerular Proteins in Primary and Bucillamine-induced Membranous Nephropathy

Kaga

Matsumura

Suzuki³

et al. 2021

Preprint

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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.

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Comparison of measurements of anti-PLA2R antibodies in Japanese patients with membranous nephropathy using in-house and commercial ELISA

Cited by 12 publications

References 27 publications

Membranous nephropathy with solitary polyclonal IgA deposition: A case report and literature review

Membranous nephropathy with solitary polyclonal IgA deposition: A case report and literature review

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

Proteomic Analysis of Glomerular Proteins in Primary and Bucillamine-induced Membranous Nephropathy

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