Autoimmunity is the result of a dysregulated immune response, typically starting in adulthood (30-40 years), mostly in women. Trigger(s) are not well understood with targeted therapy addressing the culprit of autoimmune diseases, the specific- pathological B and T-cells still missing. My research focus on the use of human monoclonal autoantibodies as tools to develop new targeted therapies and to unravel the emergence and progression of the humoral autoimmune response in thrombotic diseases. This is of upmost significant medical interest since the most effective medical interventions to balance the dysregulated immune system must address all facettes of adaptive immune response, namely the pathological autoantibodies as well as the B-cells responsible for the long-lived autoimmune response.
Emerging literature implicates autophagy, a fundamental recycling process to maintain cellular integrity and to play a vital role in determining the pathological outcomes of immune responses. We hypothesize aberrant expression of autophagy (ATG)-related genes hampers antigen-presentation, B- and T-cell survival and thus promote autoimmunity. The focus of interest is the autoimmune form of Thrombotic thrombocytopenic purpura (iTTP), a severe and life threatening disease, caused by an impaired regulation of the von Willebrand factor (VWF) multimer size due to a severe deficiency of the VWF-cleaving protease, ADAMTS13 (a distintegrin and metalloprotease with thrombospondin Type 1 motifs-13.. In a pilot study, we showed that autophagy indeed plays a role in the development and maintenance of the autoimmune status iTTP. We are interested thus, using experimental autophagy inhibitors/activators to study the impact of blocking or activating autophagy pathways on the systemic inflammation and self-antigen presentation in the acute or remission state of iTTP. With the goal to design respective autophagy modulators to improve the outcome of autoimmune patients by reprogramming the dysregulated immune response in iTTP that might be applied to other thrombotic autoimmune diseases.