Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms
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Updated: Sep 3, 2025

Granulocyte-dependent Autoantibody-induced Skin Blistering
Published on: October 12, 2012
Connor Cole1, Keshavamurthy Vinay2, Luca Borradori3
1Division of Dermatology, Rush University Medical Center, Chicago, IL, United States.
Abstract:
Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies targeting BP180 and BP230. While deposits of IgG and/or complement along the epidermal basement membrane are typically seen suggesting complement -mediated pathogenesis, several recent lines of evidence point towards complement-independent pathways contributing to tissue damage and subepidermal blister formation. Notable pathways include macropinocytosis of IgG-BP180 complexes resulting in depletion of cellular BP180, direct induction of pro-inflammatory cytokines from keratinocytes, as well as IgE autoantibody- and eosinophil-mediated effects. We review these mechanisms which open new perspectives on novel targeted treatment modalities.
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