Decoding the Complexity of Systemic Juvenile Idiopathic Arthritis

Integrative Analysis of Immunophenotype and Transcriptome in monophasic and refractory course disease

Although the management of systemic Juvenile Idiopathic Arthritis (sJIA) has significantly improved in the last few years, thanks to the efficacy of treatments with IL-6 and IL-1 inhibitors, a significant percentage, around 30%, of sJIA patients does not satisfactorily respond to the current treatment. Therefore, sJIA patients are still at risk for developing a refractory disease course and severe and life threatening complications, including macrophage activation syndrome (MAS), interstitial lung disease (ILD) and destructive arthritis. These refractory sJIA patients are challenging, no curative treatment is available, they accumulate significant morbidity and have unacceptably high mortality.

During my PhD I will focus on unravelling the mechanisms of sJIA to hasten the diagnostic process, detrimental for optimal efficacy of biologic therapy, and hopefully identifying specific molecular signatures in refractory sJIA patients, critical for the subsequent translation into novel targeted treatment strategies. To these purposes, I aim at defining cell-types and signaling pathways involved in monophasic and refractory course sJIA, evaluating the immunophenotype of the immune cells from blood samples of patients by flow cytometric assay. Besides to that, a transcriptomic-wide approach will be performed. A large Utrecht based biobank with excellent bio-samples of longitudinally sampled sJIA patients would guarantee the feasibility of the project.

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Greta Rogani