Although rheumatoid arthritis (RA) is the most intensively researched of the systemic autoimmune diseases, its pathogenesis is still not fully understood.
This is especially true for the initial events, i.e. the break in immunological tolerance that triggers the disease, leading to the activation of autoreactive T cells and the formation of autoantibodies directed in particular against citrullinated epitopes of certain proteins. The main interest of the group is therefore to investigate these processes, using both patient-derived cells and antibodies and animal models of RA.
Within the framework of this work, the characterization of human autoreactive T cells was successful, which were specifically directed against an antigen against which autoantibodies are also produced, and could thus be causally involved in the development of the disease. The findings obtained so far from animal models suggest that increased apoptosis or necrosis, i.e. cell death, in lymphoid organs could represent a decisive event in tolerance breakage. In particular, the released nucleic acids and their intracellular receptors seem to play an important role. In addition, downstream effector mechanisms are also being investigated, with synovial fibroblasts being the focus of interest.
Another focus is the investigation of the diagnostic value of autoantibodies, in particular with regard to their prognostic value with respect to the response to certain therapies. In other words, the question is whether autoantibodies can help not only in making a diagnosis, but also in making decisions regarding therapy. This question is currently being investigated in two multinational projects funded by the EU.