Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar 3;12(3):e0173201.
doi: 10.1371/journal.pone.0173201. eCollection 2017.

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

Affiliations
Free PMC article

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

Franck Pourcine et al. PLoS One. .
Free PMC article

Abstract

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.

Conflict of interest statement

Competing Interests: Rituximab was provided by Hoffmann-LaRoche. The authors confirm that they are not paid employees or consultants of Hoffmann-LaRoche, that no patents or products are in development in association with this study, and that no other perceivable competing interests exist between the authors and this company. This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the funding sources played a role in the writing of the manuscript or the decision to submit it for publication.

Figures

Fig 1
Fig 1. This flowchart depicts the patients who were enrolled in this retrospective study.
They were divided into primary membranous nephropathy (MN) and secondary MN according to the criteria described in the Methods section. Seventy-seven of the 85 patients with primary MN could be screened for anti-PLA2R antibodies (Ab+ or Ab-) and PLA2R antigen in kidney biopsy (Ag+ or Ag-). Sixty-nine patients with PLA2R-related MN as defined by the presence of PLA2R-Ab and/or Ag, were then classified according to clinical presentation with or without the nephrotic syndrome, and further subdivided according to outcome and treatment. The 8 patients with primary MN not related to PLA2R immunity were classified in the same way. The number of patients reaching CKD stage 4 is also indicated.

Similar articles

See all similar articles

Cited by 13 articles

See all "Cited by" articles

References

    1. Ponticelli C, Glassock RJ. Glomerular diseases: membranous nephropathy—a modern view. Clin J Am Soc Nephrol. 2014;9:609–616. 10.2215/CJN.04160413 - DOI - PMC - PubMed
    1. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in primary membranous nephropathy. N Engl J Med. 2009;361:11–21. 10.1056/NEJMoa0810457 - DOI - PMC - PubMed
    1. Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, et al. Prognosis of untreated patients with primary membranous nephropathy. N Engl J Med. 1993;329:85–89. 10.1056/NEJM199307083290203 - DOI - PubMed
    1. Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, et al. Spontaneous remission of nephrotic syndrome in primary membranous nephropathy. J Am Soc Nephrol. 2010;21:697–704. 10.1681/ASN.2009080861 - DOI - PMC - PubMed
    1. Donadio JV Jr, Torres VE, Velosa JA, Wagoner RD, Holley KE, Okamura M, et al. Primary membranous nephropathy: the natural history of untreated patients. Kidney Int. 1988;33:708–715. - PubMed

MeSH terms

Grant support

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.
Feedback