Autoimmunity against desmocollins in pemphigus

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IgG autoantibody responses against major non-desmoglein (Dsg) components of desmosomes, the desmocollins(Dsc), have been identified in patients with pemphigus herpetiformis, pemphigus vegetans, IgA pemphigus, as well as atypical and paraneoplastic pemphigus. While the pathogenic potential of autoantibodies specific for Dsg1 and Dsg3 has been extensively characterized, the pathogenicity of Dsc-specific IgG autoantibodies has only been demonstrated in vitro. Therefore, the work of the present workpackage is aimed at dissecting the mechanisms that regulate pathogenic Dsc-specific autoantibodies and the subsequent events that eventually lead to epidermal loss of adhesion. For this purpose, newly developed mouse models of autoimmunity against Dsc will be used. These models combine the characteristic molecular features of anti-Dsc ab-induced acantholysis with a blistering clinical phenotype and reproduce the active autoimmune response and the blistering disease induced by the immunization with the autoantigen and/or the final effector phase of the autoimmune response to Dsc (i.e., the tissue damage induced by the passive transfer of antibodies).