desmogleiinidest

Desmogleins are a family of desmosomal cadherins that mediate calcium-dependent cell–cell adhesion in epithelial tissues. In humans, four desmogleins are recognized (DSG1–DSG4). They are transmembrane glycoproteins with extracellular cadherin repeats and a cytoplasmic tail that binds desmosomal plaque proteins such as plakoglobin, plakophilin, and desmoplakin, linking to the intermediate filament cytoskeleton.

Desmogleins support mechanical integrity in tissues exposed to stress, notably the skin and mucous membranes. Expression patterns vary by tissue: DSG1 is enriched in the upper epidermis; DSG3 is more abundant in mucosal epithelia and deeper epidermal layers; DSG2 is widely expressed across many tissues; DSG4 is present in select epithelia.

Disruption of desmoglein function—whether by genetic mutation or autoimmune antibodies—can cause disease. The best-known condition is pemphigus vulgaris, typically driven by autoantibodies against DSG3 (and sometimes DSG1), leading to acantholysis and intraepidermal blistering. Pemphigus foliaceus is mainly associated with anti-DSG1 antibodies, producing superficial blisters with limited mucosal involvement. Bullous impetigo results from Staphylococcus aureus exfoliative toxins that cleave DSG1. Paraneoplastic pemphigus can involve antibodies against multiple desmosomal proteins, including desmogleins.

Diagnosis relies on immunofluorescence and serology: direct immunofluorescence shows intercellular IgG deposition in the epidermis, and ELISA can detect anti-DSG1 and anti-DSG3 antibodies. Treatment generally targets autoimmunity, typically employing immunosuppressive strategies and related biologic therapies.