Pemphigus IgG causes skin splitting in the presence of both desmoglein 1 and desmoglein 3.
According to the desmoglein (Dsg) compensation concept, different epidermal cleavage planes observed in pemphigus vulgaris and pemphigus foliaceus have been proposed to be caused by different autoantibody profiles against the desmosomal proteins Dsg 1 and Dsg 3. According to this model, Dsg 1 autoantibodies would only lead to epidermal splitting in those epidermal layers in which no Dsg 3 is present to compensate for the functional loss of Dsg 1. We provide evidence that both pemphigus foliaceus-IgG containing Dsg 1- but not Dsg 3-specific antibodies and pemphigus vulgaris-IgG with antibodies to Dsg 1 and Dsg 3 were equally effective in causing epidermal splitting in human skin and keratinocyte dissociation in vitro. These effects were present where keratinocytes expressed both Dsg 1 and Dsg 3, demonstrating that Dsg 3 does not compensate for Dsg 1 inactivation. Rather, the cleavage plane in intact human skin caused by pemphigus autoantibodies was similar to the plane of keratinocyte dissociation in response to toxin B-mediated inactivation of Rho GTPases. Because we recently demonstrated that pemphigus-IgG causes epidermal splitting by inhibition of Rho A, we propose that Rho GTPase inactivation contributes to the mechanisms accounting for the cleavage plane in pemphigus skin splitting.
Spindler
Volker
V
University of Würzburg, Institute of Anatomy and Cell Biology, Würzburg, Germany.
Drenckhahn
Detlev
D
Zillikens
Detlef
D
Waschke
Jens
J
D001323:Autoantibodies / Q000276:immunology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D051183:Desmoglein 1 / Q000235:genetics / Q000378:metabolism*; D051184:Desmoglein 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D010392:Pemphigus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D001323:Autoantibodies; C495297:DSG1 protein, human; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3; D007074:Immunoglobulin G; D020741:rho GTP-Binding Proteins