Evidence map›Paper›PMID 35326398›Full record

ArticleCells2022

Stabilization of Keratinocyte Monolayer Integrity in the Presence of Anti-Desmoglein-3 Antibodies through FcRn Blockade with Efgartigimod: Novel Treatment Paradigm for Pemphigus?

Anna Zakrzewicz, Celina Würth, Benedikt Beckert, Simon Feldhoff, Katrien Vanderheyden, Stian Foss, Jan Terje Andersen, Hans de Haard, Peter Verheesen, Vladimir Bobkov and 1 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  3. Article
  4. Article
  5. Review
  6. The therapeutic age of the neonatal Fc receptor.Nature reviews. Immunology · 2023
    Review
  7. Review
  8. In Vitro, Ex Vivo, and In Vivo Models for the Study of Pemphigus.International journal of molecular sciences · 2022
    Review
  9. Article
  10. Review
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Anna ZakrzewiczInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
Celina WürthInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
Benedikt BeckertInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
Simon FeldhoffInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
Katrien VanderheydenArgenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium.
Stian FossDepartment of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.
Jan Terje AndersenDepartment of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.
Hans de HaardArgenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium.
Peter VerheesenArgenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium.ORCID 0000-0001-8760-9158
Vladimir BobkovArgenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium.
Ritva TikkanenInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.ORCID 0000-0002-8393-1825
Justus-Liebig-Universität Gießen · DEAblynx (Belgium) · BEOslo University Hospital · NO

Funding

Deutsche Forschungsgemeinschaft TI 291/10-2
6 · The paper itself

Abstract

Pemphigus vulgaris is an autoimmune blistering disease of the epidermis, caused by autoantibodies against desmosomal proteins, mainly desmogleins 1 and 3, which induce an impairment of desmosomal adhesion and blister formation. Recent findings have shown that inhibition of immunoglobulin G binding on the neonatal Fc receptor, FcRn, results in reduced autoantibody recycling and shortens their half-life, providing a valid treatment option for PV. We have here analyzed the role of FcRn in human keratinocytes treated with antibodies isolated from pemphigus vulgaris patient or with recombinant anti-desmoglein-3 antibodies that induce pathogenic changes in desmosomes, such as loss of monolayer integrity, aberrant desmoglein-3 localization and degradation of desmoglein-3. We show that blocking IgG binding on FcRn by efgartigimod, a recombinant Fc fragment undergoing clinical studies for pemphigus, stabilizes the keratinocyte monolayer, whereas the loss of desmoglein-3 is not prevented by efgartigimod. Our data show that FcRn may play a direct role in the pathogenesis of pemphigus at the level of the autoantibody target cells, the epidermal keratinocytes. Our data suggest that in keratinocytes, FcRn may have functions different from its known function in IgG recycling. Therefore, stabilization of keratinocyte adhesion by FcRn blocking entities may provide a novel treatment paradigm for pemphigus.

Indexed as

Autoimmune DiseasesPemphigusAutoantibodiesDesmoglein 3HumansImmunoglobulin GInfant, NewbornKeratinocytesAutoantibodiesDesmoglein 3Immunoglobulin Gautoantibodiesautoimmune diseaseefgartigimodepidermisFc receptor neonatalkeratinocytespemphigus vulgaris

Identifiers

PMID35326398
PMCPMC8946243
OpenAlexW4226094998

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.