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- W2323165094 abstract "<h3>Background</h3> 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 <h3>Objectives</h3> To study first line treatment with recombinant IL-1 receptor antagonist (rIL-1RA, Anakinra) in 16 newly systemic onset JIA patients <h3>Methods</h3> 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) <h3>Results</h3> 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. <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> None Declared" @default.
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- W2323165094 date "2013-06-01" @default.
- W2323165094 modified "2023-09-23" @default.
- W2323165094 title "OP0055 IL-1 receptor antagonist restores IL-18 nk cell axis in systemic JIA" @default.
- W2323165094 doi "https://doi.org/10.1136/annrheumdis-2012-eular.1738" @default.
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