Desmoglein 3 (DSG3) (DSG3)

Desmoglein 3 (DSG3), also known as the pemphigus vulgaris antigen, is a 130 kDa transmembrane glycoprotein belonging to the cadherin family of calcium-dependent cell-adhesion molecules [1, 2]. It is primarily expressed in the basal and immediate suprabasal layers of stratified squamous epithelia, where it plays a fundamental role in maintaining tissue integrity through the formation of desmosomes [2, 7]. In the autoimmune disease pemphigus vulgaris, pathogenic IgG autoantibodies (anti-DSG3 autoantibodies) target the extracellular domain of DSG3, leading to the loss of keratinocyte adhesion (acantholysis) and subsequent blistering of the skin and mucous membranes [4, 7, 12]. Beyond its structural role, DSG3 is involved in intracellular signaling pathways, including p38 MAPK and YAP/p53 signaling, which can be dysregulated in both autoimmune and neoplastic contexts [1, 7]. Therapeutic interventions aim to reduce the levels of anti-DSG3 autoantibodies through B-cell depletion with agents like rituximab, accelerated IgG clearance with neonatal Fc receptor (FcRn) inhibitors like efgartigimod alfa, or the selective elimination of autoantibody-producing B-cell clones using chimeric autoantibody receptor T-cell (CAAR-T) therapy [1, 11, 14]. Additionally, DSG3 is overexpressed in certain cancers, such as squamous cell carcinoma, making it a potential target for antibody-based anti-tumor therapies, provided that epitope specificity is carefully managed to avoid pemphigus-like toxicities [3, 6].

Other names

Pemphigus vulgaris antigenPVADesmoglein-3 autoantibody130 kDa pemphigus vulgaris antigenCadherin family member 6CDHF6

B-cell depletion, FcRn inhibition, selective B-cell targeting (CAAR-T), non-specific immunosuppression, and neutralization/removal of pathogenic IgG