Background Systemic onset juvenile idiopathic arthritis (SoJIA) is an acquired auto-inflammatory disease characterized by systemic inflammation and innate immune activation reflected in uncontrolled production of cytokines such as IL-1, IL-6 and IL-18. In SoJIA, NK cell function is severely hampered despite high levels of IL-18. We recently found that defective phosphorylation of the IL-18 receptor beta is responsible for the deficient IL-18-NK cell axis in SoJIA
Objectives To study first line treatment with recombinant IL-1 receptor antagonist (rIL-1RA, Anakinra) in 16 newly systemic onset JIA patients
Methods Clinical outcome was measured using ACRp70 and ACRp90. Furthermore NK cell function, inflammasome activity and cytokine expression was assed during follow up (max 2 years)
Results Here we show that patients with SoJIA have increased inflammasome activation leading to elevated IL-18 levels. First line treatment with rIL-1RA effectively down-regulated IL-18 levels through suppression of inflammasome activation and led to rapid resolution of clinical features in 87% (ACRp90) of patients. Furthermore, using rIL-1RA as first line treatment approach the defective IL-18-NK cell axis is restored as shown by resulting in improved lytic NK cell function and regaining of the NK cell responsiveness to IL-18 stimulation.
Conclusions These data suggest that the mechanisms of inflammatory control induced by rIL-1RA in SoJIA patients involves more than blocking IL-1R signalling, since it seems to restore the IL-18-NK cell route and affecting the inflammasome as well.
Disclosure of Interest None Declared
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