Neutrophil Elastase and Myeloid-Related Protein-8/-14 as Executors and Regulators of Tissue Damage in Autoimmune Bullous Diseases

The prevalence of chronic inflammatory diseases, especially autoimmune disorders (AID), has increased dramatically during the last decades in the world. Most diseases require a life-long non-curative treatment which is largely limited to the application of immunosuppressive drugs. The permanent and severe reduction in the quality of life of the patients as well as the enormous economical burden associated with these diseases emphasizes the high medical need for the development of novel therapeutic options. Since many years, the contribution of the different components of immune system to the pathogenesis of AID has been under intensive investigation. In the context of autoimmune bullous diseases (AIBDs), neutrophils have been identified as essential players in the effector phase of AIBDs. Neutrophil-derived mediators are involved in tissue damage and skin blister formation which is the hallmark of AIBDs including epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP). However, although the principal participation of neutrophil proteases and ROS has clearly been shown in this course, the precise regulatory and executive mechanisms of neutrophils in the disease still remain unclear. In this study, it is hypothesized that neutrophils contribute to the effector phase by two ways, indirectly by the secretion of myeloid-related proteins (MRP)-8 and -14 leading to amplification and maintenance of the inflammatory loop as well as directly by the release of tissue-destructing elastase. Therefore, delineation of the mechanisms how neutrophils cause tissue damage will establish further information about the pathomechanisms of EBA and BP and provide a novel therapeutic avenue specifically targets the terminal phase of the disease