دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Stabilization of Keratinocyte Monolayer Integrity in the Presence of Anti-Desmoglein-3 Antibodies through FcRn Blockade with Efgartigimod: Novel Treatment Paradigm for Pemphigus?
المؤلفون: Zakrzewicz A; Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Würth C; Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Beckert B; Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Feldhoff S; Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Vanderheyden K; Argenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium., Foss S; Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.; Institute of Clinical Medicine and Department of Pharmacology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway., Andersen JT; Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.; Institute of Clinical Medicine and Department of Pharmacology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway., Haard H; Argenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium., Verheesen P; Argenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium., Bobkov V; Argenx BV, Industriepark Zwijnaarde 7, 9052 Ghent, Belgium., Tikkanen R; Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
المصدر: Cells [Cells] 2022 Mar 10; Vol. 11 (6). Date of Electronic Publication: 2022 Mar 10.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Autoimmune Diseases*/metabolism , Pemphigus*/drug therapy , Pemphigus*/metabolism, Autoantibodies ; Desmoglein 3/metabolism ; Humans ; Immunoglobulin G/metabolism ; Infant, Newborn ; Keratinocytes/metabolism
مستخلص: 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.
التعليقات: Erratum in: Cells. 2022 May 20;11(10):. (PMID: 35626757)
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معلومات مُعتمدة: TI 291/10-2 Deutsche Forschungsgemeinschaft
فهرسة مساهمة: Keywords: Fc receptor neonatal; autoantibodies; autoimmune disease; efgartigimod; epidermis; keratinocytes; pemphigus vulgaris
المشرفين على المادة: 0 (Autoantibodies)
0 (Desmoglein 3)
0 (Immunoglobulin G)
تواريخ الأحداث: Date Created: 20220325 Date Completed: 20220413 Latest Revision: 20220528
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8946243
DOI: 10.3390/cells11060942
PMID: 35326398
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells11060942