Differential transcriptional and epigenetic signatures in CD4+ T cells separate enthesitis related and psoriatic juvenile idiopathic arthritis – a pilot study

Juvenile idiopathic arthritis (JIA) is the most common musculoskeletal rheumatic disease affecting children. Following the currently used International League of Associations for Rheumatology (ILAR) classification, JIA encompasses seven clinically defined subtypes all of which share chronic inflammatory arthritis as a unifying symptom. Re-classification of JIA based on molecular signatures has been proposed and promises future patient stratification based on disease mechanisms and target-directed therapeutic interventions. This study applied flow cytometric immune cell profiling alongside mRNA expression analysis (NanoString inflammation panel) and DNA methylation profiling (Illumina EPIC450K arrays) to identify molecular signatures associated with enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (jPsA) subtypes of JIA. Disctinct gene expression and DNA methylation signatures in peripheral blood CD4 + T-cells uniquely associate with ERA versus jPsA. Disease-associated sigantures associate with immune memory, immune checkpoint disturbances, and inflammatory signaling. These exploratory findings provide preliminary evidence for molecular differences between ERA- and jPsA and support further evaluation of genetic and/or epigenetic stratification approaches in larger cohorts, to deliver towards individualised and target-directed treatments.