In total, we identified eight upregulated hub genes in patients with active SJIA: HP, MPO, MMP8, MMP9, ARG1, OLFM4, DEFA4, and PGLYRP1. We postulate these genes to be significantly involved in the inflammatory environment and subsequent disease progression in patients with active SJIA. Here, DEFA4 is linked to systemic-onset juvenile idiopathic arthritis.