Evidence map›Paper›PMID 31395435›Full record

Trial reportJournal of autoimmunity2020

Autoantigens PLA2R and THSD7A in membranous nephropathy share a common epitope motif in the N-terminal domain.

M Fresquet, S J Rhoden, T A Jowitt, E A McKenzie, I Roberts, R Lennon, P E Brenchley

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in Journal of autoimmunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. THSD7A Exacerbates Atherosclerosis via Activation of Signaling Axis αvβ3/CEBPD/IL1A.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Questions and Caveats in Antigen-Defined Membranous Nephropathy.Journal of the American Society of Nephrology : JASN · 2025
    Review
  4. Review
  5. Review
  6. Review
  7. Observational
  8. Article
  9. Review
  10. The Role of Anti-PLAInternational journal of environmental research and public health · 2022
    Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Autoimmunity in 2019.Clinical reviews in allergy & immunology · 2020
    Review
  16. Article
  17. Article
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

M FresquetWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, UK.
S J RhodenWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, UK.
T A JowittWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, UK.
E A McKenzieManchester Institute of Biotechnology, University of Manchester, UK.
I RobertsJohn Radcliffe Hospital, Oxford, UK.
R LennonWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, UK; Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
P E BrenchleyManchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: paul.brenchley@manchester.ac.uk.
University of Manchester · GBManchester University NHS Foundation Trust · GBJohn Radcliffe Hospital · GBWellcome Centre for Cell-Matrix Research · GB

Funding

Medical Research Council MR/J010847/1Wellcome Trust 097820Wellcome Trust 202860/Z/16/Z
6 · The paper itself

Abstract

Patients with membranous nephropathy have autoantibodies against PLA2R (up to 80%), or THSD7A (up to 2%). We previously described the immunodominant epitope within PLA2R but epitopes in THSD7A are still unknown. To find anti-THSD7A sera for this study, we screened 1843 sera from biopsy-proven MN patients by ELISA and identified 22 sera as anti-THSD7A positive representing 1.2% of MN cases. Anti-THSD7A positive sera were further characterized by western blotting and slot blotting on THSD7A protein fragments and peptides. Real time interaction analyses and antibodies off-rate could be reliably determined using bio-layer interferometry. A signature motif in the N-terminal domain of THSD7A (T28mer) with sequence homology to the major PLA2R epitope (P28mer) was identified. B-cell epitope prediction analysis and homology modelling revealed this sequence to be antigenic and surface available suggesting it is accessible for the antibody to bind. All ten selected sera bound to the T28mer confirming this sequence as a dominant epitope in THSD7A. Reactivity to this sequence was lost following kallikrein protease cleavage within the predicted epitope. Importantly, cross-reactivity of both PLA2R and THSD7A autoantibodies was observed at the peptide but not the protein level. We propose that this common motif shared by both autoantigens could be an epitope involved in the initial B-cell triggering event in MN.

Indexed as

AdultAgedAnimalsAutoantibodiesAutoantigensB-LymphocytesEpitopesFemaleGlomerulonephritis, MembranousHEK293 CellsHumansMaleMiceMiddle AgedReceptors, Phospholipase A2ThrombospondinsAutoantibodiesAutoantigensEpitopesPLA2R1 protein, humanReceptors, Phospholipase A2ThrombospondinsTHSD7A protein, humanAutoimmunityMembranous nephropathyPLA2RTHSD7A

Identifiers

PMID31395435
PMCPMC7471840
OpenAlexW2966766101

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.