Bullous pemphigoid (BP) is the most common autoimmune blistering disease in Europe and primarily affects elderly patients. It is caused by autoantibodies targeting hemidesmosomal proteins, mainly BP180 (type XVII collagen), which are essential for stable adhesion between the epidermis and the dermis. The resulting immune reaction leads to inflammation, loss of adhesion, and subepidermal blistering.

This project aims to uncover differences in the intracellular signaling of oral and skin keratinocytes after stimulation with BP180 autoantibodies (IgG and/or IgA), with the goal of identifying new therapeutic targets and better understanding the pathogenesis of BP and mucous membrane pemphigoid (MMP).

 Using immunostaining and Western blotting, I will compare the expression of BP180 and BP230 in a human skin keratinocyte line (HaCaT) and an oral mucosal keratinocyte line (OHK). To explore signal transduction, I will stimulate both cell types with patient-derived BP180 autoantibodies and analyze kinome activity using a chip-based kinase assay (PamGene™). Based on the identified kinases, we will test selective inhibitors to evaluate their ability to modulate the inflammatory response and cellular effects of autoantibody stimulation. The functional relevance of these inhibitors will be confirmed using cytokine release assays (e.g., IL-6, IL-8) and potentially other readouts.

 By characterizing disease-specific signaling pathways and cellular responses, this project aims to contribute to the development of mechanism-based therapies for autoimmune blistering diseases.