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Updated: May 14, 2026
12:23
Granulocyte-dependent Autoantibody-induced Skin Blistering
Published on: October 12, 2012
A pathophysiologic role for epidermal growth factor receptor in pemphigus acantholysis
Meryem Bektas1, Puneet S Jolly, Paula Berkowitz
1Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599-7287, USA.
The Journal of Biological Chemistry
|February 14, 2013
Summary
Pemphigus vulgaris (PV) IgG activates EGF receptor (EGFR) in skin cells, leading to cell damage. Inhibiting EGFR prevents PV-induced blistering, suggesting EGFR inhibitors as a potential pemphigus treatment.
Area of Science:
- Dermatology
- Immunology
- Cell Biology
Background:
- Pemphigus is an autoimmune disease targeting desmogleins (dsg1/dsg3).
- The role of epidermal growth factor receptor (EGFR) signaling in pemphigus pathogenesis is unclear.
Purpose of the Study:
- To investigate the role of EGFR in pemphigus vulgaris (PV) pathogenesis.
- To explore EGFR as a potential therapeutic target for pemphigus.
Main Methods:
- Primary human keratinocytes were treated with PV IgG.
- EGFR activation and downstream effects (dsg3 endocytosis, cell adhesion) were assessed.
- Inhibition of EGFR and p38 mitogen-activated protein kinase (p38) was performed.
- A passive transfer mouse model of pemphigus was used to evaluate blister formation.
Main Results:
- PV IgG activated EGFR in keratinocytes, downstream of p38.
- EGFR inhibition blocked PV IgG-induced dsg3 endocytosis, keratin retraction, and loss of cell adhesion.
- EGFR inhibition prevented PV IgG-induced blister formation in mice.
Conclusions:
- Cross-talk exists between dsg3 and EGFR in pemphigus pathogenesis, regulated by p38.
- EGFR is a critical mediator of PV-induced keratinocyte damage and blister formation.
- EGFR inhibitors represent a promising therapeutic strategy for pemphigus.
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