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Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways

Published:October 28, 2021DOI:https://doi.org/10.1016/j.jid.2021.04.040
      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.

      Abbreviations:

      BMZ (basement membrane zone), BP (bullous pemphigoid), BPDAI (Bullous Pemphigoid Disease Area Index), CAART (chimeric autoantibody receptor T cell), CR (complete remission), DSC (desmocollin), DSG (desmoglein), EBV (Epstein‒Barr virus), EC (extracellular cadherin), FDA (Food and Drug Administration), KC (keratinocyte), PDAI (Pemphigus Disease Area Index), PF (pemphigus foliaceus), PV (pemphigus vulgaris), SAE (serious adverse event), Th (T helper type), VH (variable heavy)
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