Desmoglein as a target in autoimmunity and infection.
Clinical phenotypes of most diseases are complex. However, once the mechanism behind the scene is clarified, the nature shows amazing beauty. There is a simple logic behind a complex disease. The exact molecular mechanism of the blister formation in staphylococcal scalded skin syndrome (SSSS) remained to be elucidated for 3 decades since exfoliative toxin was discovered by Melish and Glasgow in 1970. A knowledge accumulated to understand the pathogenesis of pemphigus and cell-cell adhesion of keratinocytes led us to solve this question. Desmoglein 1, which is a cadherin type cell-cell adhesion molecule in desmosomes, is targeted in two different skin diseases, pemphigus foliaceus, and SSSS. In pemphigus foliaceus IgG autoantibodies are developed against desmoglein 1 and inhibit its adhesive function with resultant blister formation in the superficial epidermis. In SSSS, exfoliative toxin produced by Staphylococcus aureus specifically binds and cleaves desmoglein 1 with resultant blister formation at the identical site.
Amagai
Masayuki
M
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, USA. amagai@sc.itc.keio.ac.jp
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D003598:Cytoskeletal Proteins / Q000276:immunology*; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015394:Molecular Structure; D010392:Pemphigus / Q000276:immunology* / Q000503:physiopathology; D013206:Staphylococcal Scalded Skin Syndrome / Q000276:immunology*
D003598:Cytoskeletal Proteins; C495297:DSG1 protein, human; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D007074:Immunoglobulin G