Desmoglein 1 (DSG1) and Desmoglein 3 (DSG3) (DSG1/3)

Keratinocyte intercellular adhesion proteins, primarily represented by the desmoglein family (DSG1 and DSG3), are essential transmembrane glycoproteins that form the core of desmosomes, the specialized junctions responsible for strong cell-cell adhesion in the epidermis. These proteins belong to the cadherin superfamily and mediate calcium-dependent adhesion between adjacent keratinocytes, ensuring the structural integrity of the skin and mucous membranes. In autoimmune diseases such as pemphigus vulgaris and pemphigus foliaceus, autoantibodies target these proteins, leading to the loss of adhesion (acantholysis) and the formation of life-threatening blisters. Therapeutic strategies focus on reducing the levels of these pathogenic autoantibodies through B-cell depletion (e.g., rituximab) or FcRn inhibition (e.g., efgartigimod), as well as experimental approaches like chimeric autoantibody receptor (CAAR) T-cell therapy designed to specifically eliminate autoreactive B cells.

Other names

Keratinocyte intercellular adhesion proteinsDesmosomal cadherinsPemphigus antigensDSG1DSG3Desmocollin

B-cell depletion, inhibition of neonatal Fc receptor (FcRn) to increase IgG clearance, systemic immunosuppression, and targeted chimeric autoantibody receptor T-cell therapy.