Evaluation of the molecular determinants of primary immunodeficiency in adult patients, pathogenesis of STAT1 gain-of-function and evaluation of gene therapeutic approaches.

Primary immunodeficiencies (PIDs) have provided crucial information for the elucidation of immunological pathways. Although many causal mutations in PID patients have been identified, the exact pathogenesis often remains to be elucidated and clues for an individualized therapeutic approach remain absent. In this project we focus on adult patients with a confirmed or suspected primary immunodeficiency. We explore a genetic cause in patients lacking a molecular diagnosis. Next, we explore in depth the pathophysiology of STAT1 gain-of-function in order to find novel treatment options. Finally, we setup a platform for evaluation of gene therapeutic approaches for monogenic, rare, PIDs in adults. Thereby, we hope to answer an unmet need: personalized medicine for rare diseases accompanied by significant morbidity and mortality, currently lacking rationalized and/or etiological treatment options.