Induction of experimental epidermolysis bullosa acquisita by immunization with murine collagen VII

Abstract

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease caused by an autoreactive response against collagen VII, the major constituent of the anchoring fibrils at the epidermal basement membrane. The pathogenic relevance of collagen VII-specific autoantibodies has been conclusively demonstrated ex vivo and in experimental animals using antibody passive transfer models. To study the mechanisms of autoantibody production and tissue damage an animal model reproducing both the autoimmune response and the active skin disease is needed. In the present protocol, we describe the induction of an autoimmune response and active disease by immunizing mice with recombinant murine collagen VII and the analysis of the induced disease phenotype. The humoral and cellular immune response elicited in mice by immunization with the autoantigen, as well as the induced skin pathology replicate the features of the human disease at the clinical, histo- and immunopathological levels. Thus, this model is an excellent tool for investigating the mechanisms underlying pathogenic autoantibody production, the autoantibody-mediated tissue injury, and for the development of more effective therapeutic strategies in autoimmune diseases.