CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Autoimmune diseases (ADs) are chronic inflammatory disorders affecting approx. 8% of the population in industrialized countries. The pathogenesis of ADs is still poorly understood. Current concepts suggest an interplay between genetic and diverse non-genetic factors leading to a dysregulated immune response directed against self-structures. Strategies for the treatment of ADs are only partially effective, unspecific, and still largely rely on systemic immunosuppression which is associated with serious side-effects.Pemphigoid diseases (PDs) are a group of prototypical antibody-mediated ADs manifesting on skin and adjacent mucous membranes. PDs are a growing health burden, predominantly affect the elderly, and are sharply rising in incidence. They are associated with a considerably increased mortality rate and patients often succumb to side-effects of immunosuppression. The autoantigens of PDs are clearly defined, and the pathological significance of autoantibodies targeting these autoantigens has been unequivocally demonstrated. However, the mechanisms of the initial break of tolerance, the gradual evolution of autoreactivity towards the abundant production of pathogenic autoantibodies, and the mechanisms regulating the recruitment and activity of inflammatory cells in the skin are, like for most other ADs, only poorly understood. The clearly established cause– effect relationship between autoantibodies and disease combined with the exposition of inflammation on the body surface, allowing continuous monitoring and manipulation, as well as the establishment of robust preclinical models and large patient cohorts, render PDs superb paradigm diseases to decipher the pathomechanisms of antibody-mediated ADs.Exploiting these advantages, in its first funding period, PANTAU will focus on two milestones in the pathogenesis of PDs: (i) the transition of non-pathogenic into pathogenic, but clinically still inapparent autoimmunity and (ii) the subsequent transition of clinically inapparent autoimmunity into overt disease. Delineating these transitions will be instrumental to selectively disrupt them and to establish new treatments for PDs and, perspectively, also or other antibody-mediated ADs. PDs are the scientific focus of a new research building for the Center for Research on Inflammation of the Skin (CRIS) that is currently constructed on the Lübeck campus with funding through the federal government and the state of Schleswig-Holstein according to article 91b of the German constitution. The establishment of the CRC 1526 will greatly benefit from this development and will further promote it.