Skip to main content

Advertisement

SpringerLink
Log in

Definition of a new cut-off for the anti-phospholipase A2 receptor (PLA2R) autoantibody immunoassay in patients affected by idiopathic membranous nephropathy

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Autoantibodies against phospholipase A2 receptor (PLA2R) are a sensitive and specific marker for idiopathic membranous nephropathy (IMN). The aim of our study was to redefine the cut-off value for the measurement of anti-PLA2R autoantibody levels by an automated enzyme immunoassay, in a large single-center cohort of Italian IMN patients at the time of diagnosis. Sixty-seven consecutive incident patients, with biopsy-proven IMN, were recruited. All patients were naïve to preceding immunosuppressive therapeutic regimens. The patient population had a mean age of 57 years and included 48 males and 19 females. Also, 200 patients with other renal diseases and 36 healthy subjects were studied as controls. The anti-PLA2R autoantibody levels were measured using the commercial enzyme-linked immunosorbent assay kit at the time of renal biopsy. At a cut-off value of 2.7 RU/ml (significantly lower than the manufacturer’s recommended value of 14 RU/ml), calculated by receiver operating characteristic curves, the sensitivity and specificity of anti-PLA2R autoantibodies in the diagnosis of IMN was 88.1 and 96% respectively. The adapted cut-off value of 2.7 UI/ml increased sensitivity without affecting the specificity and it should be the recommended value for this method. Additionally our study confirmed the correlation, at baseline, between anti-PLA2R autoantibody levels and other biomarkers of disease activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. McGrogan A, Franssen CF, de Vries CS (2011) The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant 26(2):414–430

    Article  Google Scholar 

  2. Ronco P, Debiec H (2012) Pathogenesis of membranous nephropathy: recent advances and future challenges. Nat Rev Nephrol 28(4):203–213

    Article  Google Scholar 

  3. Glassock RJ (2013) Pathogenesis of membranous nephropathy: a new paradigm in evolution. Contrib Nephrol 181:131–142

    Article  Google Scholar 

  4. Beck LH Jr, Salant DJ (2014) Membranous nephropathy: from models to man. J Clin Investig 124(6):2307–2314

    Article  CAS  Google Scholar 

  5. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ (2009) M-type phospholipase A2 receptors target antigen in idiopathicmembranousnephropathy. N Engl J Med 361(1):11–21

    Article  CAS  Google Scholar 

  6. Sinico RA, Mezzina N, Trezzi B, Ghiggeri GM, Radice A (2016) Immunology of membranous nephropathy: from animal models to humans. Clin Exp Immunol 183(2):157–165

    Article  CAS  Google Scholar 

  7. Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, Remuzzi G (1993) Prognosis of untreated patients with primary membranous nephropathy. N Engl J Med 329(2):85–89

    Article  CAS  Google Scholar 

  8. Polanco N, Gutierrez E, Covarsı A, Ariza F, Carreño A, Vigil A, Baltar J, Fernández-Fresnedo G, Martín C, Pons S, Lorenzo D, Bernis C, Arrizabalaga P, Fernández-Juárez G, Barrio V, Sierra M, Castellanos I, Espinosa M, Rivera F, Oliet A, Fernández-Vega F, Praga M (2010) Spontaneous remission of nephrotic syndrome in primary membranous nephropathy. J Am Soc Nephrol 21(4):697–704

    Article  CAS  Google Scholar 

  9. Donadio JV Jr, Torres VE, Velosa JA, Wagoner RD, Holley KE, Okamura M, Ilstrup DM, Chu CP (1988) Primary membranous nephropathy: the natural history of untreated patients. Kidney Int 33(3):708–715

    Article  Google Scholar 

  10. Radhakrishnan J, Cattran DC (2012) The KDIGO practice guideline on glomerulonephritis:reading between the (guide)lines application to the individual patient. Kidney Int 82(8):840–856

    Article  Google Scholar 

  11. East L, Isacke CM (2002) The mannose receptor family. Biochim Biophys Acta 1572(2–3):364–386

    Article  CAS  Google Scholar 

  12. Hoxha E, Harendza S, Zahner G, Panzer U, Steinmetz O, Fechner K, Helmchen U, Stahl RA (2011) An immunofluorescence test for phospholipase-A2-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant 26(8):2526–2532

    Article  CAS  Google Scholar 

  13. Radice A, Pieruzzi F, Trezzi B, Ghiggeri G, Napodano P, D’Amico M, Stellato T, Brugnano R, Ravera F, Rolla D, Pesce G, Giovenzana ME, Londrino F, Cantaluppi V, Pregnolato F, Volpi A, Rombolà G, Moroni G, Ortisi G, Sinico RA (2018) Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases. J Nephrol 31(2):271–278

    Article  CAS  Google Scholar 

  14. Hofstra JM, Debiec H, Short CD, Pellé T, Kleta R, Mathieson PW, Ronco P, Brenchley PE, Wetzels JF (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23(10):1735–1743

    Article  CAS  Google Scholar 

  15. Timmermans SA, Damoiseaux JG, Heerings-Rewinkel PT, Ayalon R, Beck LH Jr, Schlumberger W, Salant DJ, van Paassen P, Tervaert JW (2014) Evaluation of anti-PLA2R1 as measured by a novel ELISA in patients with idiopathic membranous nephropathy: a cohort study. Am J Clin Pathol 142(1):29–34

    Article  Google Scholar 

  16. Behnert A, Schiffer M, Muller-Deile J, Beck LH Jr, Mahler M, Fritzler MJ (2014) Antiphospholipase A(2) receptor autoantibodies: a comparison of three different immunoassays for the diagnosis of idiopathic membranous nephropathy. J Immunol Res 2014:143274

    Article  Google Scholar 

  17. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, EggersP, Van Lente F, Greene T, Coresh J (2009) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  Google Scholar 

  18. Dorfman DD, Berbaum KS, Metz CE (1992) Receiver operating characteristic rating analysis. Generalization to the population of readers and patients with the jackknife method. Investig Radiol 27(9):723–731

    Article  CAS  Google Scholar 

  19. Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, Salant DJ, Liu Z (2011) Anti- phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 22(6):1137–1143

    Article  CAS  Google Scholar 

  20. Dou Y, Zhang L, Liu D, Wang C, Quan S, Ma S, Cheng JXG, Liu Z, Zhao Z (2016) The accuracy of the anti phospholipase A2 receptor antibody in the diagnosis of idiopathic membranous nephropathy: a comparison of different cutoff values as measured by the ELISA method. Int Urol Nephrol 48(6):845–849

    Article  CAS  Google Scholar 

  21. Liu Y, Li X, Ma C, Wang P, Liu J, Su H, Zhuo H, Kong X, Xu D, Xu D (2018) Serum anti-PLA2R antibody as a diagnostic biomarker of idiopathic membranous nephropathy: the optimal cut-off value for Chinese patients. Clin Chim Acta 476:9–14

    Article  CAS  Google Scholar 

  22. de Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC (2016) A proposal for a serology-based approach to membranous nephropathy. J Am Soc Nephrol 28(2):421–430

    Article  Google Scholar 

  23. Prunotto M, Carnevali ML, Candiano G, Murtas C, Bruschi M, Corradini E, Trivelli A, Magnasco A, Petretto A, Santucci L, Mattei S, Gatti R, Scolari F, Kador P, Allegri L, Ghiggeri GM (2010) Autoimmunity in membranous nephropathy targets aldose reductase and SOD2. J Am Soc Nephrol 21(3):507–519

    Article  CAS  Google Scholar 

  24. Bruschi M, Carnevali ML, Murtas C, Candiano G, Petretto A, Prunotto M, Gatti R, Argentiero L, Magistroni R, Garibotto G, Scolari F, Ravani P, Gesualdo L, Allegri L, Ghiggeri GM (2011) Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: alfa-enolase and borderline antigens. J Proteom 74(10):2008–2017

    Article  CAS  Google Scholar 

  25. Tomas NM, Beck LH Jr, Meyer-Schwsinger C, Seitz-Polski B, Ma H, Zahner G, Dolla G, Hoxha E, Helmchen U, Dabert-Gay AS, Debayle D, Merchant M, Klein J, Salant DJ, Stahl R, Lambeau G (2014) Thrombospondin type-1 domain-containing7A in idiopathic membranous nephropathy. N Engl J Med 371:2277–2287

    Article  Google Scholar 

  26. Murtas C, Ghiggeri GM (2016) Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms. J Nephrol 29(4):469–478

    Article  CAS  Google Scholar 

  27. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ (2011) Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 6(6):1286–1291

    Article  CAS  Google Scholar 

  28. Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson FB, Cosio FG, Cattran DC, Salant DJ (2011) Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol 22(8):1543–1550

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Euroimmun Italia and Mrs Palladino Gaetanella for technical assistance.

Author information

Authors and Affiliations

  1. General Pathology Unit, Department of Biomedical Sciences and Human Oncology, University “Aldo Moro” of Bari, Bari, Italy

    Marilina Tampoia, Francesca Migliucci, Letizia Abbracciavento & Ruggiero Fumarulo

  2. Division of Nephrology, Azienda Ospedaliero-Universitaria Policlinico, Bari and University “Aldo Moro” of Bari, Piazza G. Cesare, 11, 70124, Bari, Italy

    Chiara Villani, Michele Rossini, Loreto Gesualdo & Vincenzo Montinaro

Authors
  1. Marilina Tampoia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Migliucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chiara Villani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Letizia Abbracciavento
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michele Rossini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruggiero Fumarulo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Loreto Gesualdo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vincenzo Montinaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincenzo Montinaro.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tampoia, M., Migliucci, F., Villani, C. et al. Definition of a new cut-off for the anti-phospholipase A2 receptor (PLA2R) autoantibody immunoassay in patients affected by idiopathic membranous nephropathy. J Nephrol 31, 899–905 (2018). https://doi.org/10.1007/s40620-018-0533-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-018-0533-z

Keywords

Search

Navigation