Role of desmoglein-3 domains in the pathogenesis of pemphigus

Pemphigus is a group of autoimmune bullous dermatoses affecting the skin and/or mucous membranes, with potentially fatal outcome. The most frequent clinical form is pemphigus vulgaris (PV), which is characterized by IgG circulating in the blood and fixed in the epidermis, directed against desmoglein-3 (Dsg3) in mucous membrane lesions and desmoglein-1 (Dsg1) in skin lesions. Dsg3 consists of five extracellular domains (EC1-EC5), which normally provide strong adhesion of adjacent molecules of neighboring cells to each other. The important role of Dsg3 and its individual extracellular domains, primarily EC1 and EC2, in the initiation of the autoimmune process and the formation of the clinical phenotype of the disease is described. The variability of antibody pathogenicity depending on their domain specificity can be used as a marker to assess the prognosis of the disease and opens new possibilities for the development of targeted therapeutic strategies.