In vitro and in vivo models to investigate the pathomechanisms and novel treatments for pemphigoid diseases.

Abstract

Pemphigoid diseases (PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the dermal-epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients. PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis of PDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models of PD have been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis of PDs. We summarize spontaneously arising PD in animals and the induction of PD by transfer of (auto)antibodies, transfer of (auto)-antigen-specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects of PD pathogenesis, for example loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aimed to foster translational biomedical research, to deepen our understanding of PD pathogenesis and to develop novel treatments for patients suffering from these life-threatening and difficult-to-treat autoimmune diseases.