Experimental models of epidermolysis bullosa acquisita

Abstract

Epidermolysis bullosa acquisita (EBA) is an organ-specific autoimmune disease with a well-defined antigen-autoantibody system. Recently, mutually complementary ex vivo and animal models were developed for this disease. The blister formation of EBA can be reproduced by passively transferring antibodies against type VII collagen into mice. In addition, the Fc-dependent interaction of autoantibodies with granulocytes resulting in dermal-epidermal separation can be studied using patient autoantibodies and leukocytes from healthy donors in cryostat sections of normal human skin. Finally, the autoimmune response and the active blistering disease are replicated by immunizing mice with autologous type VII collagen. The results obtained using these experimental systems provided conclusive evidence that EBA is an antibody-mediated autoimmune disease. In addition, these models represent powerful new tools for understanding EBA pathophysiology and will likely offer unique opportunities to investigate the molecular mechanisms of antibody-mediated autoimmune diseases in general. Thus, due to improved disease modelling, EBA emerges as an exquisitely instructive model disease to study fundamental, biologically and clinically crucial aspects of antibody-mediated organ-specific autoimmune diseases that extend well beyond the limits of autoimmunity against type VII collagen. The new mechanistic insights gained from investigating EBA pathogenesis will facilitate the design of immunomodulatory interventions for this and other pathogenetically related organ-specific, antibody-dependent autoimmune diseases.