title: Desmoglein 3, its pathogenecity and a possibility for therapeutic target in pemphigus vulgaris.
abstract: BACKGROUND
  Desmoglein 3 (Dsg3) is one of desmosomal cadherins and functions in epidermal keratinocyte adhesion. IgG anti-Dsg3 autoantibodies are detected in pemphigus vulgaris, an autoimmune bullous disease showing blisters and erosions on the skin and oral mucosa. Other types of pemphigus also show anti-Dsg3 antibodies. Genetic disease of Dsg3 has not been reported.
  
  
  METHODS
  Many in vitro and in vivo studies have indicated pathogenic role of anti-Dsg3 antibodies. Blisters in pemphigus vulgaris are thought to be developed by loss of keratinocyte adhesions by binding of anti-Dsg3 antibodies to Dsg3 through steric hindrance, internalization of Dsg3, changes in molecular integrity or signal transduction. There are pathogenic and nonpathogenic anti-Dsg3 antibodies reactive with different epitopes. Recent studies of pemphigus vulgaris include existence of non-Dsg3 autoantibodies, B cells and T cells reactive with Dsg3, involvement of TNF-α and IL-1 and activation of intracellular signaling.
  
  
  CONCLUSIONS
  Although systemic corticosteroids and immunosuppressive agents are mainstays for treatment of pemphigus, intravenous immunoglobulin, plasmapheresis, immunoadsorption, rituximab and TNF-α inhibitors are emerging. Anti-Dsg3 antibody-targeting therapies are reported in mouse model, but they are not yet available clinically. Clarification of pathogenic role of anti-Dsg3 antibodies in pemphigus should provide us with safer and more effective therapies.
authors.affiliation: Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Department of Dermatology, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuruta
authors.forename: Bungo
authors.initials: B
authors.lastname: Ohyama
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Chika
authors.initials: C
authors.lastname: Ohata
authors.forename: Minao
authors.initials: M
authors.lastname: Furumura
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion; D051184:Desmoglein 3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D003896:Desmosomes; D006801:Humans; D010392:Pemphigus / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000906:Antibodies; D051184:Desmoglein 3