Treatment-naïve polyarticular JIA patients displayed enhanced IFN-γ signaling in CD4 T cells and monocytes. Naïve CD4 T cells had more strongly phosphorylated STAT1 and STAT3 as compared to monocytes, which displayed increased phosphorylation of STAT3 compared with controls. This suggests that attenuation of IFN-γ signaling could be a novel alternative therapy for polyarticular JIA. This evidence concerns the gene STAT3 and polyarticular juvenile idiopathic arthritis.