TP1: Modulation of experimental epidermolysis bullosa acquisita towards an improved phenotype by initiating the production of non-pathogenic autoantibodies

Epidermolysis bullosa acquisita (EBA) is a skin-specific autoimmune disease associated with tissue injury and subepidermal blisters. Blister formation is induced by binding of IgG autoantibodies to type VII collagen which is involved in skin cell-matrix adhesion. In an experimental mouse model of this disease, type VII collagen-specific autoantibodies of the IgG subclasses IgG1 and 2 are induced by immunizing mice with murine type VII collagen. Interestingly, only the binding of the complement-fixing autoantibodies of the IgG2 subclass to type VII collagen induces the cascade of inflammatory events that lead to blister formation in the skin. In this PhD project, the mechanisms that induce either non-pathogenic IgG1 or pathogenic IgG2 autoantibodies will be explored by using a broad range of immunological methods. Subsequently, the course of the disease will be improved by preferentially inducing non-pathogenic autoantibodies.

This approach was not successful in a therapeutic setting. Hence, this project is not pursued further. During the work on this project, the focus shifted towards investigation of effects of the adaptive immune system during blistering; which is also the focus of the ongoing PhD project of S. Maass.