Pemphigus foliaceus IgG causes dissociation of desmoglein 1–containing junctions without blocking desmoglein 1 transinteraction
Jens Waschke, … , Detlef Zillikens, Detlev Drenckhahn
Jens Waschke, … , Detlef Zillikens, Detlev Drenckhahn
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3157-3165. https://doi.org/10.1172/JCI23475.
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Research Article Dermatology

Pemphigus foliaceus IgG causes dissociation of desmoglein 1–containing junctions without blocking desmoglein 1 transinteraction

Abstract

Autoantibodies against the epidermal desmosomal cadherins desmoglein 1 (Dsg1) and Dsg3 have been shown to cause severe to lethal skin blistering clinically defined as pemphigus foliaceus (PF) and pemphigus vulgaris (PV). It is unknown whether antibody-induced dissociation of keratinocytes is caused by direct inhibition of Dsg1 transinteraction or by secondary cellular responses. Here we show in an in vitro system that IgGs purified from PF patient sera caused cellular dissociation of cultured human keratinocytes as well as significant release of Dsg1-coated microbeads attached to Dsg-containing sites on the keratinocyte cellular surface. However, cell dissociation and bead release induced by PF-IgGs was not caused by direct steric hindrance of Dsg1 transinteraction, as demonstrated by single molecule atomic force measurements and by laser trapping of surface-bound Dsg1-coated microbeads. Rather, our experiments strongly indicate that PF-IgG–mediated dissociation events must involve autoantibody-triggered cellular signaling pathways, resulting in destabilization of Dsg1-based adhesive sites and desmosomes.

Authors

Jens Waschke, Paola Bruggeman, Werner Baumgartner, Detlef Zillikens, Detlev Drenckhahn

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Figure 5

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Characterization of cell-to-bead contacts induced by Dsg1-coated beads. ...
Characterization of cell-to-bead contacts induced by Dsg1-coated beads. Scanning electron microscopy (A) and transmission electron microscopy (B) were used to characterize contacts between HaCaT cells and Dsg1-coated beads formed after 30 minutes of settlement. Finger-like processes were present underneath beads with direct contact to HaCaT cells (arrows). These processes were similar to the desmosome-bearing processes found at contact sites between neighboring cells (arrowhead). Scale bars: 2.5 μm (A), 1.25 μm (A, inset); 1.0 μm (B).