Pemphigus

Pemphigus is a group of autoimmune bullous diseases of the skin and mucous membranes, which are characterized by IgG autoantibodies against desmogelin 3 (Dsg3) and/or Dsg1. Recent molecular biology techniques such as the phage display system allowed us to isolate monoclonal antibodies from peripheral blood of patients with pemphigus and to characterize their pathogenic activities and their epitopes on desmogleins. Through these studies, hot epitopes as well as a characteristic consensus sequence of CDR3 regions of pathogenic antibodies were identified. Concurrently, an active disease mouse model of pemphigus was developed by adoptive transfer of peripheral lymphocytes from Dsg3 ^-/- mice. Dsg3-specific CD4⁺ T cells were isolated from pemphigus model mice and, subsequently, Dsg3-specific T cell receptor (TCR) transgenic mice were generated. These studies have revealed that Dsg3-specific CD4⁺ T cells were able to induce, notn only antibody production with B cells and acantholysis, but also interface dermatitis. These studies have provided better understanding of pathophysiological mechanisms for pemphigus as well as deep insights for T-cell-mediated inflammatory skin diseases.