PEMPHIGUS · Pemphigus - From autoimmunity to disease

Pemphigus is a potentially lethal bullous disease of the skin and mucosa and may be considered as a paradigmatic organ-specific autoimmune disease due to 1) its well-defined autoantigens, 2) the knowledge of critical events of its immune pathogenesis and 3) the reproducibility of major clinical and pathogenic features in suitable animal models. Overall, understanding the etiopathogenesis of pemphigus may provide crucial additional insight into basic mechanisms leading from autoimmunity to autoimmune disease and may help to design more specific therapeutic strategies. Despite the enormous progress, no specific therapy is currently available in pemphigus. The present project arises as a joined effort of European Scientists and Clinicians to establish a Consortium of groups engaged in providing a critical mass of patients and research tools to address the following goals: 1) to better define the immune pathogenesis of pemphigus utilizing two in vivo models of pemphigus with emphasis on autoaggressive T cells and their collaboration with autoantibody (autoAb) secreting B cells. 2) analysis of the autoAb-driven effector phase frequently involving “epitope spreading” which ultimately leads to a more severe disease; 3) characterization of the molecular events following Ab binding to the target autoantigens by defining autoAb-induced signalling events in epidermal keratinocytes; 4) spectrum of the autoimmune B cell response and the impact of therapeutic strategies on the cellular and humoral autoimmune response in pemphigus utilizing human monoclonal Ab which will be analysed for their fine specificity and genetically and functionally characterized; and 5) clinical read-out parameters for prospective studies which are urgently needed as valid parameters for the extent and activity of disease and which will be compared to serological markers and life quality assessment in pemphigus.