Personalized medicine to tackle immune dysfunction in refractory juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic disease affecting about 1 in 1000 children.

While therapeutic options have increased, a substantial proportion of patients do not achieve remission, resulting in a lifelong disease. Our consortium will focus on children with resistant disease and high-risk outcome.

Our unique advantage is the availability of well-established longitudinal cohorts in Canada, the Netherlands, Germany, Sweden and Italy, with detailed phenotypic and biologic data collected in a standardized manner.

Our research program will include systems-immunology analyses of cellular mechanisms, novel computational methods and socio-economic modeling.

We will identify subgroups of children in our cohorts and  prospectively perform deep immune-phenotyping and single cell transcriptome analysis of immune cells of blood and arthritic joints in therapy-refractory patients together with multiomic data (genomic, transcriptomic, proteomic). Evaluation of novel disease markers and cross-validation of recently identified markers (S100A12) will be performed.

Additionally, we will characterize regional differences in access to immunomodulatory medications.

The consortium will identify key pathways – both biologic, clinical and societal which predict patients who are of particular risk for developing poor outcome.

This is the first stop towards a personalized medicine approach to tailor individualized strategies to improve outcome for affected children.