ERA-Net E-Rare

Systemic juvenile idiopathic arthritis (sJIA) is a rare, multifactorial disease which is one of the gravest chronic diseases in childhood. In addition, sJIA is associated with a life-threatening complication called macrophage activation syndrome. There is no treatment available which can cure sJIA. We have shown that an extraordinarily high expression of the alarmins S100A8 and S100A9 plays a central role in the pathogenesis of sJIA. Recently we have identified peptide sequences of about 15 amino acids within these S100-molecules which are responsible for activation of leukocytes via binding to Toll-like receptor-4 (TLR4). In this proposal we will produce novel therapeutic antibodies specifically inhibiting the S100-TLR4 interaction sites. Since release of alarmins is an initial mechanism during inflammation in sJIA targeting molecules of this family is a very promising strategy to control inflammatory processes especially of the innate immune system at a very early stage. Treat-AID incorporates experts covering all inflammatory mechanisms relevant in sJIA and well acknowledged clinical partners. The network has a unique collection of cellular and animal models to analyse therapeutic antibodies developed in this project. In conclusion, we have identified a unique and well defined target structure for anti-inflammatory therapies which is highly relevant in sJIA and which activity is restricted to local sites of inflammation minimizing the risk of systemic side effects.