ArticleJournal of the American Society of Nephrology : JASN2015
Identification of a major epitope recognized by PLA2R autoantibodies in primary membranous nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- Pooled it
- Efficacy of leflunomide combined with prednisone for the treatment of PLA2R-associated primary membranous nephropathy.Renal failure · 2020Trial
- Autoantigens PLA2R and THSD7A in membranous nephropathy share a common epitope motif in the N-terminal domain.Journal of autoimmunity · 2020Trial
- Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy.Journal of the American Society of Nephrology : JASN · 2018Trial
- Atomistic scattering modeling of the solution structure of human dimeric IgA1 reveals a structural and mechanistic basis for IgA nephropathy.The Journal of biological chemistry · 2026Article
- Animal models of idiopathic membranous nephropathy: Recent advances and future perspectives.Animal models and experimental medicine · 2026Review
- Research Advances in Rituximab-Resistant Membranous Nephropathy.Kidney medicine · 2026Review
- Beyond Titers: Phospholipase A2 Receptor Epitope Complexity as a New Lens in Membranous Nephropathy.Journal of the American Society of Nephrology : JASN · 2026Article
- Mapping of Phospholipase A2 Receptor Epitopes in Idiopathic Membranous Nephropathy and Clinical Relevance of Epitope Profiles.Journal of the American Society of Nephrology : JASN · 2026Article
- Preclinical evaluation of antigen-specific B-cell depletion for phospholipase A2 receptor membranous nephropathy with chimeric autoantibody receptor T cells.Kidney international · 2026Article
- Treatment strategies for rituximab-resistant primary membranous nephropathy: from resistance mechanisms to emerging therapies.Frontiers in immunology · 2026Review
- Identification of antibodies against phospholipase A2 receptor peptides in PLA2R-associated membranous nephropathy with negative circulating anti-PLA2R antibodies.Frontiers in immunology · 2026Article
- The personalized approach to rituximab treatment in membranous nephropathy: a multi-center randomized controlled trial.EClinicalMedicine · 2025Article
- Clinical outcomes of immunosuppressive therapy in patients with seronegative anti-PLA2R antibodies and PLA2R-related membranous nephropathy.Clinical and experimental nephrology · 2025Article
- Laser Microdissection and Mass Spectrometry Reveals Diverse Membranous Nephropathy Antigens.Kidney international reports · 2025Article
- Detection and prognostic relevance of PLA2R epitopes in idiopathic membranous nephropathy: a simultaneous quantitative multiplex suspension array detection method.Clinical kidney journal · 2025Article
- Role of PLA2R domain antibodies and epitope spreading in risk stratification and prediction of proteinuria remission in primary membranous nephropathy.Scientific reports · 2025Article
- Membranous Nephropathy.Journal of clinical medicine · 2025Review
- Membranous nephropathy in Kimura disease: A case report and literature review on renal biopsy findings.Clinical nephrology. Case studies · 2025Article
- Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies.Renal failure · 2024Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Phospholipase A2 receptor 1 (PLA2R) is a target autoantigen in 70% of patients with idiopathic membranous nephropathy. We describe the location of a major epitope in the N-terminal cysteine-rich ricin domain of PLA2R that is recognized by 90% of human anti-PLA2R autoantibodies. The epitope was sensitive to reduction and SDS denaturation in the isolated ricin domain and the larger fragment containing the ricin, fibronectin type II, first and second C-type lectin domains (CTLD). However, in nondenaturing conditions the epitope was protected against reduction in larger fragments, including the full-length extracellular region of PLA2R. To determine the composition of the epitope, we isolated immunoreactive tryptic fragments by Western blotting and analyzed them by mass spectrometry. The identified peptides were tested as inhibitors of autoantibody binding to PLA2R by surface plasmon resonance. Two peptides from the ricin domain showed strong inhibition, with a longer sequence covering both peptides (31-mer) producing 85% inhibition of autoantibody binding to PLA2R. Anti-PLA2R antibody directly bound this 31-mer peptide under nondenaturing conditions and binding was sensitive to reduction. Analysis of PLA2R and the PLA2R-anti-PLA2R complex using electron microscopy and homology-based representations allowed us to generate a structural model of this major epitope and its antibody binding site, which is independent of pH-induced conformational change in PLA2R. Identification of this major PLA2R epitope will enable further therapeutic advances for patients with idiopathic membranous nephropathy, including antibody inhibition therapy and immunoadsorption of circulating autoantibodies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.