Role of Anti-mouse PLA2R1 ELISA in Membranous Nephropathy

NCT02199145 | Completed

• 1 other identifier: 14-AOI-05
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

Brief Summary

Membranous Nephropathy (MN) is an auto-immune kidney disease and a common cause of nephrotic syndrome. About 30% of MN patients progress to end-stage kidney disease (ESKD) while 30% undergo spontaneous remission. The phospholipase A2 receptor (PLA2R1) is the major auto-antigen in idiopathic MN. Anti-PLA2R1 autoantibodies are found during the active phase of MN. Predictors of disease progression include high titers of anti-PLA2R1 autoantibodies and serum creatinine levels at presentation, as well as decline in renal function during the first six months of follow-up. Investigators identified new prognostic factors in a cohort of 41 idiopathic MN patients with nephrotic syndrome and anti-PLA2R1 autoantibodies at the time of presentation. During a follow-up of at least 36 months, 21 patients had a persistent nephrotic syndrome (group A) and 20 showed partial or total remission (group R). We first measured the cross-reactivity of their sera at the time of presentation to human, rabbit and mouse recombinant PLA2R1 by western blot. All patients exhibited reactivity against human and rabbit PLA2R1, but only some of them did against mouse PLA2R1. These results suggest the presence of distinct epitopes that are differentially conserved among PLA2R1 orthologs.Investigators then set-up three parallel ELISAs using human, rabbit and mouse recombinant PLA2R1. All 41 MN patients showed activity in human and rabbit ELISAs at presentation but only 32 of them (78%) in mouse ELISA.They finally analyzed the association between anti-PLA2R1 titers at presentation in the different ELISAs and the subsequent clinical outcome. The mean anti-PLA2R1 activity was significantly different between group A and R in mouse ELISA but not in human and rabbit ELISA. Patients with anti-mouse PLA2R1 activity over 605 RU (relative unit)/ml showed a significantly lower survival without doubling of serum creatinine or ESKD , but patients in the highest tertile of anti-PLA2R1 activity in rabbit and human ELISA did not show a significant increased risk of renal failure progression. The results suggest that the specific detection of particular anti-PLA2R1 autoantibodies using the novel anti-mouse PLA2R1 ELISA can identify MN patients at risk for ESKD. The aim is to confirm these result on a prospective cohort.

Conditions

Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• Change from baseline Creatininemia level

  30% increase in creatininemia after 6 months of symptomatic treatment with RAAS blocker

  at 6, 12 and 18 months

Secondary Outcomes (1)

• Remission rate in MN

  at 12 months

Study Arms (1)

Blood and urine analysis

OTHER

creatinine, albumin, blood electrolytes, proteinuria /creatinine in sample 1 assay Ac anti-PLA2R1 on 3 ELISA (human, rabbit and mouse)

Procedure: Blood and urine analysis

Interventions

Blood and urine analysis PROCEDURE

creatinine, albumin, blood electrolytes, proteinuria / creatinine in sample 1 assay Ac anti-PLA2R1 on 3 ELISA (human, rabbit and mouse)

Blood and urine analysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients
• Patients with MN stade I-II confirmed by kidney biopsy
• Patients with MDRD\>30 ml/mn/1.73m2
• Patients with anti-PLA2R1 antibodies
• Effective Contraception for women of childbearing age

You may not qualify if:

• Patients minors
• Patients refusing to participate in the study
• Patients with secondary MN (systemic Lupus, hepatitis B virus, hepatitis C virus or cancer)
• Pregnant women: a urine pregnancy test will be performed for women of childbearing age. The results will be communicated to the patient by a doctor of his choice.
• Persons deprived of liberty (administrative or judicial)
• Persons under guardianship
• People may not understand the research
• Persons under guardianship, under judicial protection

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (3)

CHU de Besançon

Besançon, France

Location

AP-HM

Marseille, 13354, France

Location

Nephrology Department, Nice University Hospital

Nice, 06003, France

Location

Related Publications (2)

• Seitz-Polski B, Dahan K, Debiec H, Rousseau A, Andreani M, Zaghrini C, Ticchioni M, Rosenthal A, Benzaken S, Bernard G, Lambeau G, Ronco P, Esnault VLM. High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy. Clin J Am Soc Nephrol. 2019 Aug 7;14(8):1173-1182. doi: 10.2215/CJN.11791018. Epub 2019 Jul 24.

  PMID: 31340979 RESULT

• Teisseyre M, Cremoni M, Boyer-Suavet S, Crepin T, Benzaken S, Zorzi K, Esnault V, Brglez V, Seitz-Polski B. Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy. Front Immunol. 2021 Oct 13;12:738788. doi: 10.3389/fimmu.2021.738788. eCollection 2021.

  PMID: 34721403 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Blood Specimen Collection; Urinalysis

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Study Officials

• Barbara SEITZ-POLSKI, PhD

  Nice University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 24, 2014
• Study Start: July 17, 2015
• Primary Completion: June 4, 2020
• Study Completion: June 4, 2020
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

FR (3)