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Biochimie. 2015 Nov;118:104-15. doi: 10.1016/j.biochi.2015.08.007. Epub 2015 Aug 19.

Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1 antigens and development of two novel ELISAs with different diagnostic performances in idiopathic membranous nephropathy.

Author information

1
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice-Sophia Antipolis, Valbonne Sophia-Antipolis, France; Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, France; Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, France. Electronic address: seitz-polski.b@chu-nice.fr.
2
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice-Sophia Antipolis, Valbonne Sophia-Antipolis, France.
3
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice-Sophia Antipolis, Valbonne Sophia-Antipolis, France; University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
4
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice-Sophia Antipolis, Valbonne Sophia-Antipolis, France; Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, France; Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, France.
5
Service de Néphrologie Dialyse Transplantation Rénale, CHU Hôpital Nord, Saint-Etienne, and Université de Saint-Etienne PRES Université de Lyon, Saint-Etienne, France.
6
Service de Néphrologie, CHU de Strasbourg, Strasbourg, France.
7
Service de Néphrologie Dialyse Transplantation Rénale, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, UMR S1076, Université Aix-Marseille, Marseille, France.
8
Service de Néphrologie Dialyse Transplantation Rénale, CHU Saint-Jacques, Besançon, France.
9
EUROIMMUN AG, Lübeck, Germany.
10
Centre de Recherche Clinique, Hôpital l'Archet, Université de Nice-Sophia Antipolis, France.
11
Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, France.
12
Service de Néphrologie, Hôpital Pasteur, Université de Nice-Sophia Antipolis, France.
13
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice-Sophia Antipolis, Valbonne Sophia-Antipolis, France. Electronic address: lambeau@ipmc.cnrs.fr.

Abstract

About 70% of patients with idiopathic membranous nephropathy (iMN) have autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m) PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active disease or in drug-induced remission. In contrast, only 51% of patients were reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti-PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1 orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an independent predictor of clinical outcome in multivariate analysis (p = 0.009), and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of patients (12 patients) had a poor renal outcome (p < 0.001). A similar threshold could not be defined in hPLA2R1 and rbPLA2R1 ELISAs. We conclude that rbPLA2R1 is an alternative antigen to hPLA2R1 to measure anti-PLA2R1 in active disease while mPLA2R1 is a unique antigen that can detect a subset of anti-PLA2R1 autoantibodies present at high levels (>605 RU/mL) only in iMN patients at risk of poor prognosis, and is thus useful to predict iMN outcome.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01897961.

KEYWORDS:

Autoimmunity; Conformational epitope; ELISA; Membranous nephropathy; Mouse PLA2R1; Orthologs; PLA2R1 autoantibodies; Rabbit PLA2R1

PMID:
26296473
DOI:
10.1016/j.biochi.2015.08.007
[Indexed for MEDLINE]

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