Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years

PLoS One. 2017 Mar 3;12(3):e0173201. doi: 10.1371/journal.pone.0173201. eCollection 2017.


Introduction: Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers.

Methods: In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status.

Results: Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria.

Conclusion: Assessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Anti-Idiotypic / immunology
  • Antigens / blood*
  • Antigens / immunology
  • Autoimmunity*
  • Biopsy
  • ErbB Receptors / blood
  • Female
  • Glomerulonephritis, Membranous / blood*
  • Glomerulonephritis, Membranous / immunology
  • Glomerulonephritis, Membranous / pathology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Proteinuria / blood
  • Proteinuria / immunology
  • Receptors, Phospholipase A2 / blood*
  • Receptors, Phospholipase A2 / immunology
  • Serum Albumin / metabolism
  • Thrombospondins / blood
  • Thrombospondins / immunology


  • Antibodies, Anti-Idiotypic
  • Antigens
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2
  • Serum Albumin
  • THSD7A protein, human
  • Thrombospondins
  • EGFR protein, human
  • ErbB Receptors

Grants and funding

This study was funded by grants from the European Research Council ERC-2012-ADG_20120314 (Grant Agreement 322947) and from 7th Framework Programme of the European Community Contract 2012-305608 (European Consortium for High-Throughput Research in Rare Kidney Diseases). Rituximab was provided by Hoffmann–La Roche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.