Pemphigus vulgaris is an autoantibody-mediated blistering skin disease affecting the stratified squamous epithelium. Patient skin and mucous membranes are often affected simultaneously. The disease is caused through IgG autoantibodies directed against cell surface desmosomal adhesion molecules, which are found in between neighbouring cells. Targeting desmosomes leads to a loss of keratinocyte cell adhesion, thus resulting in suprabasilar blistering of the epidermis of the skin and/or mucous membranes (i.e., acantholysis). Specifically, the IgG-autoantibodies are reacting against the desmosomal cell cadherins Desmoglein 1 (Dsg1) and Desmoglein 3 (Dsg3).

The project will concentrate on testing an antibody phage display-derived, well-characterized bispecific monoclonal antibody in form of a single-chain variable-region fragment (scFv). This Dsg3/1-reactive monoclonal antibody was already found to be directly pathogenic in ex vivo human skin organ culture, requiring no activation of cells via Fc receptors. Very interestingly it also displayed cross-reactivity to murine tissue by immunofluorescence testing. Therefore we here set out to administer this scFv into adult mice, allowing to study pathophysiology and potential treatment options in murine systems.

Currently studies are limited to testing pemphigus antibodies in neonatal murine models, thus impeding the transferability of conclusions from rodent to human. If an adult mouse model with mucocutaneous skin lesions can be established, the next step would involve the testing of various novel compounds thought to improve the disease outcome of pemphigus vulgaris.