Evidence map›Paper›PMID 25205735›Full record

ArticleJournal of the American Society of Nephrology : JASN2015

Identification of the immunodominant epitope region in phospholipase A2 receptor-mediating autoantibody binding in idiopathic membranous nephropathy.

Liyo Kao, Vinson Lam, Meryl Waldman, Richard J Glassock, Quansheng Zhu

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

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 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
9.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Contemporary Perspectives on Chronic Renal Disorders.Chronic diseases and translational medicine · 2025
    Review
  15. Article
  16. Membranous Nephropathy.Journal of clinical medicine · 2025
    Review
  17. Review
  18. Review
  19. Article
  20. Review

19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Liyo KaoDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; and.
Vinson LamDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; and.
Meryl WaldmanClinical Research Center, National Institute of Diabetes and Digestive and Kidney Diseases/Kidney Disease Section, National Institutes of Health, Bethesda, Maryland.
Richard J GlassockDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; and.
Quansheng ZhuDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; and quzhu@mednet.ucla.edu.
University of California, Los Angeles · USNational Institutes of Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Recent clinical studies established that >70% of patients with idiopathic (also called primary) MN (IMN) possess circulating autoantibodies targeting the M-type phospholipase A2 receptor-1 (PLA2R) on the surface of glomerular visceral epithelial cells (podocytes). In situ, these autoantibodies trigger the formation of immune complexes, which are hypothesized to cause enhanced glomerular permeability to plasma proteins. Indeed, the level of autoantibody in circulation correlates with the severity of proteinuria in patients. The autoantibody only recognizes the nonreduced form of PLA2R, suggesting that disulfide bonds determine the antigenic epitope conformation. Here, we identified the immunodominant epitope region in PLA2R by probing isolated truncated PLA2R extracellular domains with sera from patients with IMN that contain anti-PLA2R autoantibodies. Patient sera specifically recognized a protein complex consisting of the cysteine-rich (CysR), fibronectin-like type II (FnII), and C-type lectin-like domain 1 (CTLD1) domains of PLA2R only under nonreducing conditions. Moreover, absence of either the CysR or CTLD1 domain prevented autoantibody recognition of the remaining domains. Additional analysis suggested that this three-domain complex contains at least one disulfide bond required for conformational configuration and autoantibody binding. Notably, the three-domain complex completely blocked the reactivity of autoantibodies from patient sera with the full-length PLA2R, and the reactivity of patient sera with the three-domain complex on immunoblots equaled the reactivity with full-length PLA2R. These results indicate that the immunodominant epitope in PLA2R is exclusively located in the CysR-FnII-CTLD1 region.

Indexed as

AutoantibodiesCysteineFibronectinsGlomerulonephritis, MembranousHEK293 CellsHumansImmunodominant EpitopesLectins, C-TypePodocytesReceptors, Phospholipase A2AutoantibodiesCysteineFibronectinsImmunodominant EpitopesLectins, C-TypeReceptors, Phospholipase A2immunology and pathologymembranous nephropathypathophysiology of renal disease and progression

Identifiers

PMID25205735
PMCPMC4310656
OpenAlexW2145486852

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.