The incidence of paediatric immune-mediated diseases is increasing globally, with a notably younger age of onset. High-dose glucocorticoids (GC) remain the most accessible and commonly used anti-inflammatory treatment for these conditions. However, evidence-based guidance for pulse GC therapy is limited, particularly regarding the optimal dosage and duration, and the ability to predict patient responsiveness and toxicity. Moreover, epigenetic, metabolic, and immunological sequelae of high-dose GC in children remain poorly understood. In this EP PerMed project, we are conducting a multi-centre, multi-omics study to compare the clinical efficacy and long-term outcomes of a 3-day vs. 5-day pulse of high-dose GC in children with acute immunemediated disorders. We will collect data at three timepoints: (I) baseline, (II) 3-days after first GC pulse, and (III) at 3-month follow-up. We will link clinical, conventional laboratory, patient reported outcomes (PROs), and genomic information with systems-level analyses of transcriptomic, proteomic, metabolic, and epigenetic changes. The goal is to identify biomarkers that predict individual response and risk of toxicity, and to lay the groundwork for evidence-based treatment algorithms integrating alternative targeted therapies when GC is likely to be ineffective or harmful. This project is a collaboration between paediatric specialists, immunologists, systems biologists, patient representatives (KOURIR), and bioethicists. We anticipate delivering a robust predictive framework and guidelines that can be rapidly translated into clinical practice, thereby personalising treatment approaches for acutely ill children with immune-mediated diseases.

The consortium is still under contract negotiations and changes may occur.

Funding from Saxon State Ministry for Science, Culture and Tourism (SMWK) via PathoNext GmbH.