AUTHOR=Cole Connor , Vinay Keshavamurthy , Borradori Luca , Amber Kyle T. 

TITLE=Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.912876

DOI=10.3389/fimmu.2022.912876

ISSN=1664-3224

ABSTRACT=<p>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.</p>