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Correction: Zakrzewicz et al. Stabilization of Keratinocyte Monolayer Integrity in the Presence of Anti-Desmoglein-3 Antibodies through FcRn Blockade with Efgartigimod: Novel Treatment Paradigm for Pemphigus? Cells 2022, 11, 942
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Correction published on 20 May 2022, see Cells 2022, 11(10), 1700.
Article

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

1
Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany
2
Argenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium
3
Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
4
Institute of Clinical Medicine and Department of Pharmacology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Laurent Misery
Cells 2022, 11(6), 942; https://doi.org/10.3390/cells11060942
Received: 26 November 2021 / Revised: 1 March 2022 / Accepted: 8 March 2022 / Published: 10 March 2022 / Corrected: 20 May 2022
(This article belongs to the Special Issue Autoimmune Diseases: Molecular Mechanisms and Therapies)
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. View Full-Text
Keywords: keratinocytes; epidermis; pemphigus vulgaris; autoimmune disease; autoantibodies; Fc receptor neonatal; efgartigimod keratinocytes; epidermis; pemphigus vulgaris; autoimmune disease; autoantibodies; Fc receptor neonatal; efgartigimod
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MDPI and ACS Style

Zakrzewicz, A.; Würth, C.; Beckert, B.; Feldhoff, S.; Vanderheyden, K.; Foss, S.; Andersen, J.T.; Haard, H.d.; Verheesen, P.; Bobkov, V.; Tikkanen, R. Stabilization of Keratinocyte Monolayer Integrity in the Presence of Anti-Desmoglein-3 Antibodies through FcRn Blockade with Efgartigimod: Novel Treatment Paradigm for Pemphigus? Cells 2022, 11, 942. https://doi.org/10.3390/cells11060942

AMA Style

Zakrzewicz A, Würth C, Beckert B, Feldhoff S, Vanderheyden K, Foss S, Andersen JT, Haard Hd, Verheesen P, Bobkov V, Tikkanen R. Stabilization of Keratinocyte Monolayer Integrity in the Presence of Anti-Desmoglein-3 Antibodies through FcRn Blockade with Efgartigimod: Novel Treatment Paradigm for Pemphigus? Cells. 2022; 11(6):942. https://doi.org/10.3390/cells11060942

Chicago/Turabian Style

Zakrzewicz, Anna, Celina Würth, Benedikt Beckert, Simon Feldhoff, Katrien Vanderheyden, Stian Foss, Jan Terje Andersen, Hans de Haard, Peter Verheesen, Vladimir Bobkov, and Ritva Tikkanen. 2022. "Stabilization of Keratinocyte Monolayer Integrity in the Presence of Anti-Desmoglein-3 Antibodies through FcRn Blockade with Efgartigimod: Novel Treatment Paradigm for Pemphigus?" Cells 11, no. 6: 942. https://doi.org/10.3390/cells11060942

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