Altered signaling in systemic juvenile idiopathic arthritis monocytes

- sJIA CD14 monocytes show specific, defective STAT1 phosphorylation downstream of IFNs.
- sJIA monocytes express higher transcript levels of the IFN signaling inhibitor SOCS1.
- Recent changes in medication use in sJIA may alter the IFN hyporesponsiveness.
- Impaired IFN/pSTAT1 signaling consistent with monocyte skewing away from M1 phenotype
- Impaired IFN/pSTAT1 signaling may contribute to disease pathology in sJIA.

Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation and arthritis. Monocytes are implicated in sJIA pathogenesis, but their role in disease is unclear. The response of sJIA monocytes to IFN may be dysregulated. We examined intracellular signaling in response to IFN type I (IFNα) and type II (IFNγ) in monocytes during sJIA activity and quiescence, in 2 patient groups. Independent of disease activity, monocytes from Group 1 (collected between 2002 and 2009) showed defective STAT1 phosphorylation downstream of IFNs, and expressed higher transcript levels of SOCS1, an inhibitor of IFN signaling. In the Group 2 (collected between 2011 and 2014), monocytes of patients with recent disease onset were IFNγ hyporesponsive, but in treated, quiescent subjects, monocytes were hyperresponsive to IFNγ. Recent changes in medication in sJIA may alter the IFN hyporesponsiveness. Impaired IFN/pSTAT1 signaling is consistent with skewing of sJIA monocytes away from an M1 phenotype and may contribute to disease pathology.