The role of S100A12 as trigger and promoter of immunological phenomenons is studied on mouse as well as primary human cells. In this context we aim to understand the relevance of extracellular S100A12 in diseases as systemic idiopathic juvenile arthritis (SIJA) and Familial Mediterranean Fever (FMF). SJIA is one of the most severe systemic inflammatory diseases in childhood. Many patients show frequent flares or persistent disease activity with significant morbidity and serious complications, especially those children with a therapy-resistant course. SJIA can be assigned to the group of autoinflammatory diseases . FMF resembles a prototype of a group of rare inherited autoinflammatory syndromes characterized by recurrent, self-limited episodes of fever and inflammation. During inflammatory attacks serum levels of S100A12 are massively elevated, comparable to levels found in SJIA. In different projects, we are currently studying the role of extracellular S100A12 in the diseases’ pathology regarding various parameters such as 1) receptor usage and biochemistry, 2) redundancies with other calgranulins and 3) blocking strategies.
As the protein is exclusively expressed in humans, functional preclinical in vivo studies are hampered to date. To allow for those, we are currently generating transgenic S100A12 mice, which specifically overexpress the protein in immune cells.