Compared with male patients, female patients with systemic juvenile idiopathic arthritis (JIA) have higher levels of genes related to circulating immature neutrophils, with these genes being associated with response to treatment, according to study results published in Journal of Leukocyte Biology.

The prevalence of systemic JIA has been estimated to be 3 times higher in female than male patients; female patients were also found to have lower rates of response to treatment.

The aim of the current study was to characterize blood gene signatures of 3 cohorts of male and female patients with JIA and assess the effect of sex on the whole blood transcriptomes of patients.

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Researchers included clinical metadata from 451 patients and analyzed whole blood transcriptomic data of those with and without systemic JIA. They performed differential expression analyses for male and female patients, separately.

The number of differentially expressed genes was similar in male and female patients with systemic JIA compared with sex-matched control participants. However, because most differentially expressed genes were not shared between males and female patients, researchers suggested sexual dimorphism of systemic JIA at a molecular level.

There were a total of 44 genes whose fold-change expression was much higher in female vs male patients with systemic JIA compared with control participants. Of these genes, 18 were associated with neutrophil functions (adjusted P <.0001). In comparison, a total of 47 genes were highly induced in male patients with systemic JIA. Several of the genes associated with neutrophil functions were specific for female patients and were not expressed in male patients with systemic JIA.

Among the 44 genes in systemic JIA female-specific signature, 9 were highly expressed in neutrophil progenitor cells, suggesting that circulating immature neutrophils may be more positively activated or in higher numbers in female vs male patients with systemic JIA.

The potential effect of patient sex on levels of immature neutrophils in response to treatment with anti-interleukin-1 (anakinra) was assessed by comparing the expression of band neutrophils signature in female and male patients with systemic JIA after treatment. The data suggest that while in male patients there was no change in band neutrophils signature, in female patients compared with healthy control participants, the expression of band neutrophils was higher; expression of band neutrophils was even higher after the first month of treatment and only went down after 6 months of treatment.

Data also suggest that that this immature neutrophil signature is sexually dimorphic across the 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,” the researchers concluded.


Prada-Medina CA, Peron JPS, Nakaya HI. Immature neutrophil signature associated with the sexual dimorphism of systemic juvenile idiopathic arthritis. Published online August 13, 2020. J Leukoc Biol. doi:10.1002/JLB.6MA0720-015RR