Article Text

OP0055 IL-1 receptor antagonist restores IL-18 nk cell axis in systemic JIA
  1. W. De Jager,
  2. S.J. Vastert,
  3. B.J. Noordman,
  4. B.J. Prakken,
  5. N.M. Wulffraat
  1. Pediatric Immunology, Uuniversity Medical Center Utrecht, Utrecht, Netherlands


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

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.