Testing the Effect of Kinase Inhibitors in the Human Skin Organ Culture (HSOC) Model for Pemphigus Foliaceus

Pemphigus foliaceus (PF) is an autoimmune blistering skin disease related to the more common pemphigus vulgaris (PV). In PV, autoantibodies target desmosomal adhesion molecules desmoglein (dsg) 1 and 3, leading to intraepithelial split formation. This process, known as acantholysis, clinically manifests as vesicles and erosions in the skin and mucous membranes resulting in scaling and bleeding. PF is distinguished by autoantibodies that exclusively target dsg1, affecting only the outer skin, not the mucous membranes. Lesions typically appear in seborrheic areas such as the upper trunk, face and scalp, where subcorneal blister formation leads to puff pastry-like lesions.

Current treatments for PF include high-dose systemic corticosteroids, immunoapheresis of circulating autoantibodies and intravenous immunoglobulins, including the anti-CD20 antibody Rituximab. However, no targeted treatments have been established yet. This project aims to determine whether PF shares a similar pathomechanism with PV and to clarify the role of kinases in this process. The HSOC model for PF replicates intraepidermal split formation by introducing a specific single-chain variable fragment (scFv). My goal is to evaluate the effectiveness of kinase inhibitors using this HSOC model for PF.