Cargando…
Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience
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 qu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036194/ https://www.ncbi.nlm.nih.gov/pubmed/33123964 http://dx.doi.org/10.1007/s40620-020-00888-w |
_version_ | 1783676856071880704 |
---|---|
author | Porcelli, Brunetta Guarnieri, Andrea Ferretti, Fabio Garosi, Guido Terzuoli, Lucia Cinci, Francesca Tabucchi, Antonella Tampoia, Marilina Abbracciavento, Letizia Villani, Chiara Deleonardi, Gaia Grondona, Ana Gabriela Mazzolini, Marcello La Manna, Gaetano Santostefano, Marisa Infantino, Maria Manfredi, Mariangela Spatoliatore, Giuseppe Rosati, Alberto Somma, Chiara Bizzaro, Nicola |
author_facet | Porcelli, Brunetta Guarnieri, Andrea Ferretti, Fabio Garosi, Guido Terzuoli, Lucia Cinci, Francesca Tabucchi, Antonella Tampoia, Marilina Abbracciavento, Letizia Villani, Chiara Deleonardi, Gaia Grondona, Ana Gabriela Mazzolini, Marcello La Manna, Gaetano Santostefano, Marisa Infantino, Maria Manfredi, Mariangela Spatoliatore, Giuseppe Rosati, Alberto Somma, Chiara Bizzaro, Nicola |
author_sort | Porcelli, Brunetta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8036194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-80361942021-04-27 Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience Porcelli, Brunetta Guarnieri, Andrea Ferretti, Fabio Garosi, Guido Terzuoli, Lucia Cinci, Francesca Tabucchi, Antonella Tampoia, Marilina Abbracciavento, Letizia Villani, Chiara Deleonardi, Gaia Grondona, Ana Gabriela Mazzolini, Marcello La Manna, Gaetano Santostefano, Marisa Infantino, Maria Manfredi, Mariangela Spatoliatore, Giuseppe Rosati, Alberto Somma, Chiara Bizzaro, Nicola J Nephrol Original Article 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. Springer International Publishing 2020-10-29 2021 /pmc/articles/PMC8036194/ /pubmed/33123964 http://dx.doi.org/10.1007/s40620-020-00888-w Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Porcelli, Brunetta Guarnieri, Andrea Ferretti, Fabio Garosi, Guido Terzuoli, Lucia Cinci, Francesca Tabucchi, Antonella Tampoia, Marilina Abbracciavento, Letizia Villani, Chiara Deleonardi, Gaia Grondona, Ana Gabriela Mazzolini, Marcello La Manna, Gaetano Santostefano, Marisa Infantino, Maria Manfredi, Mariangela Spatoliatore, Giuseppe Rosati, Alberto Somma, Chiara Bizzaro, Nicola Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience |
title | Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience |
title_full | Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience |
title_fullStr | Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience |
title_full_unstemmed | Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience |
title_short | Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience |
title_sort | diagnostic accuracy of anti-phospholipase a2 receptor (pla2r) antibodies in idiopathic membranous nephropathy: an italian experience |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036194/ https://www.ncbi.nlm.nih.gov/pubmed/33123964 http://dx.doi.org/10.1007/s40620-020-00888-w |
work_keys_str_mv | AT porcellibrunetta diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT guarnieriandrea diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT ferrettifabio diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT garosiguido diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT terzuolilucia diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT cincifrancesca diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT tabucchiantonella diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT tampoiamarilina diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT abbracciaventoletizia diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT villanichiara diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT deleonardigaia diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT grondonaanagabriela diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT mazzolinimarcello diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT lamannagaetano diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT santostefanomarisa diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT infantinomaria diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT manfredimariangela diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT spatoliatoregiuseppe diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT rosatialberto diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT sommachiara diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience AT bizzaronicola diagnosticaccuracyofantiphospholipasea2receptorpla2rantibodiesinidiopathicmembranousnephropathyanitalianexperience |