043 A novel tool to analyse the pathogenic impact of IgG binding to extracellular domain 5 of Desmoglein 3

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease characterized by autoantibodies (auto-ab) against the desmosomal adhesion molecules desmoglein3 (Dsg3) and Dsg1. Binding of Dsg specific auto-ab to target structures induces an interruption integrity which ultimately results in clinical manifestation flaccid blisters erosions PV patients. Underlying mechanisms inducing blister formation upon binding Dsg-specific are largely unknown. Numerous studies demonstrated pathogenicity for amino-terminal region (extracellular domain 1, EC1) Dsg3. However, Dsg3 response patients polyclonal, including directed both amino- membrane proximal epitopes. In this study, murine monoclonal antibody membrane-proximal (EC5) ectodomain was analysed. This Dsg3-specific isolated from supernatant B-cell hybridoma tested various specificity functional assays as well in-vivo. Results clearly demonstrate that specifically binds human capable inhibiting intercellular keratinocyte accompanied activation p38 MAPK signal transduction pathway. Here, first time, we can EC5 exhibit pathogenic activity similar EC1-specific AK23 without Ca2+ dependency. Our deliver new aspects more defined understanding auto-ab-induced PV.