For many autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA), the molecular mechanisms remain elusive. JIA can be used as a model to study autoimmune disease as immune cells can be taken directly from the site of inflammation. To create a better insight into these mechanisms, we aimed to assess both the epigenetic and transcriptomic profile of JIA patient-derived cells. As both the CD4+T cells and monocytes are known to contribute to this disease ChIP-seq and RNA-seq were performed on both cell populations. We hypothesize that epigenetic and transcriptomic profiling can contribute to a better understanding of JIA pathogenesis, the identification of novel disease contributing cellular pathways and possibly new therapeutic targets.

Methods:

CD4+CD45RO+ T cells and CD14+ monocytes were FACS sorted from the blood of healthy controls and the blood and synovial fluid of five oligo JIA patients. Transcriptomic analysis was performed on both cell types using RNA-sequencing. To identify active enhancers ChIP-sequencing was performed for H3K27Ac, a marker associated with higher transcription.

Results:

Analysis of the active enhancer profile (ChIP-seq) of JIA patient cells demonstrated thousands of disease-associated differences, which corresponded to disease-associated gene expression (RNA-seq). Strikingly, arthritis-associated SNPs were significantly enriched in JIA enhancers, illustrating the importance of these non-coding regions for disease pathogenesis. Presently, we are genetically manipulating the top twenty of the target genes that we identified to further assess their role in JIA.

Conclusion:

These results demonstrate that active enhancers directly contribute to disease-associated gene expression, and identified many genes that could contribute to disease pathogenesis. Our data might provide novel therapeutic targets for the treatment of JIA.