Evidence map›Paper›PMID 32815159›Full record

ArticleBritish journal of pharmacology2020

Identification of novel therapeutic targets for blocking acantholysis in pemphigus.

Imke A K Burmester, Sarah Flaswinkel, Clara-Sophie Thies, Anika Kasprick, Mayumi Kamaguchi, Valéria Bumiller-Bini, Shirin Emtenani, Nick Feldmann, Khalaf Kridin, Enno Schmidt and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Dsg3 epitope-specific signalling in pemphigus.Frontiers in immunology · 2023
    Article
  8. Article
  9. In Vitro, Ex Vivo, and In Vivo Models for the Study of Pemphigus.International journal of molecular sciences · 2022
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
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

15 authors.

Imke A K BurmesterLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Sarah FlaswinkelLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Clara-Sophie ThiesLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Anika KasprickLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Mayumi KamaguchiLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Valéria Bumiller-BiniLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.ORCID 0000-0003-4000-2417
Shirin EmtenaniLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Nick FeldmannLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Khalaf KridinLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Enno SchmidtLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Nina van BeekDepartment of Dermatology, University of Lübeck, Lübeck, Germany.
Detlef ZillikensDepartment of Dermatology, University of Lübeck, Lübeck, Germany.
Christoph M HammersDepartment of Dermatology, University of Lübeck, Lübeck, Germany.
Jennifer E HundtLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Ralf J LudwigLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.ORCID 0000-0002-1394-1737

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Deutsche Forschungsgemeinschaft EXC 2167-390884018 EXC 306 GRK 1727 EXC 2167
6 · The paper itself

Abstract

background and purposePemphigus is caused by autoantibodies against desmoglein (Dsg) 1, Dsg3, and/or non-Dsg antigens. Pemphigus vulgaris (PV) is the most common manifestation of pemphigus, with painful erosions on mucous membranes. In most cases, blistering also occurs on the skin, leading to areas of extensive denudation. Despite improvements in pemphigus treatment, time to achieve remission is long, severe adverse events are frequent and 20% of patients do not respond adequately. Current clinical developments focus exclusively on modulating B cell function or autoantibody half-life. However, topical modulation of PV autoantibody-induced blistering is an attractive target because it could promptly relieve symptoms. EXPERIMENTAL APPROACH: To address this issue, we performed an unbiased screening in a complex biological system using 141 low MW inhibitors from a chemical library. Specifically, we evaluated PV IgG-induced Dsg3 internalization in HaCaT keratinocytes. Validation of the 20 identified compounds was performed using keratinocyte fragmentation assays, as well as a human skin organ culture (HSOC) model. KEY

resultsOverall, this approach led to the identification of four molecules involved in PV IgG-induced skin pathology: MEK1, TrkA, PI3Kα, and VEGFR2. CONCLUSION AND IMPLICATIONS: This unbiased screening revealed novel mechanisms by which PV autoantibodies induce blistering in keratinocytes and identified new treatment targets for this severe and potentially life-threatening skin disease.

Indexed as

PemphigusAcantholysisAutoantibodiesDesmoglein 3HumansKeratinocytesAutoantibodiesDesmoglein 3autoimmunitycell signalingmodel systempemphigusskin

Identifiers

PMID32815159
PMCPMC7588822

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.