Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways

Pemphigus and pemphigoid are paradigms for understanding the mechanisms of antibody-mediated autoimmune disease in humans. In pemphigus, IgG4-predominant autoantibodies cause intraepidermal blistering by direct interference with desmoglein interactions and subsequent disruption of desmosomes and signaling pathways. In pemphigoid, IgG1, IgG4, and IgE autoantibodies against basement membrane zone antigens directly interfere with hemidesmosomal adhesion, activating complement and Fc receptor-mediated effector pathways. Unraveling disease mechanisms in pemphigus and pemphigoid has identified numerous opportunities for clinical trials, which hold promise to identify safer and more effective therapies for these potentially life-threatening diseases.

Automated summary

Pemphigus and pemphigoid serve as models for understanding antibody-mediated autoimmune diseases in humans. Pemphigus is caused by IgG4 autoantibodies interfering with desmoglein interactions, while pemphigoid is caused by autoantibodies interfering with hemidesmosomal adhesion. Unraveling the mechanisms of these diseases has opened up opportunities for clinical trials to discover safer and more effective therapies.