Desmoglein 3, its pathogenecity and a possibility for therapeutic target in pemphigus vulgaris

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.

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.

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.