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.
AuthorsVolker Spindler, Detlev Drenckhahn, Detlef Zillikens, Jens Waschke
JournalThe American journal of pathology (Am J Pathol) Vol. 171 Issue 3 Pg. 906-16 (Sep 2007) ISSN: 0002-9440 [Print] United States
PMID17640963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • DSG1 protein, human
  • DSG3 protein, human
  • Desmoglein 1
  • Desmoglein 3
  • Immunoglobulin G
  • rho GTP-Binding Proteins
  • Autoantibodies (immunology)
  • Cell Adhesion (physiology)
  • Cell Line
  • Desmoglein 1 (genetics, metabolism)
  • Desmoglein 3 (genetics, metabolism)
  • Humans
  • Immunoglobulin G (immunology)
  • Keratinocytes (cytology, metabolism)
  • Pemphigus (immunology, metabolism, pathology)
  • Skin (cytology, metabolism, pathology)
  • rho GTP-Binding Proteins (antagonists & inhibitors, metabolism)

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