Immature neutrophil signature associated with the sexual dimorphism of systemic juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a group of inflammatory conditions of unknown etiology whose incidence is sex dependent. Although several studies have attempted to identify JIA-related gene signatures, none have systematically assessed the impact of sex on the whole blood transcriptomes of JIA patients. By analyzing over 400 unique pediatric gene expression profiles, we characterized the sexual differences in leukocyte composition of systemic JIA patients and identified sex-specific gene signatures that were related to immature neutrophils. Female systemic JIA patients presented higher activation of immature neutrophil-related genes compared to males, and these genes were associated with the response to IL-1 receptor blockade treatment. Also, we found that this immature neutrophil signature is sexually dimorphic across human lifespan and in adults with rheumatoid arthritis and asthma. These results suggest that neutrophil maturation is sexually dimorphic in rheumatic inflammation, and that this may impact disease progression and treatment.