Systemic juvenile idiopathic arthritis: New insights into pathogenesis and cytokine directed therapies

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is considered as a polygenic autoinflammatory disease. The prominent systemic clinical features, the marked elevation of inflammatory markers, and the absence of autoantibodies make this disease very different from the other juvenile idiopathic arthritis (JIA) forms. Innate immune mechanisms appear to play a central role: the overproduction of inflammatory cytokines of innate immunity is a typical feature of sJIA. Increased understanding of the role of these cytokines has been translated into therapeutic approaches. Indeed, remarkable results have been observed with interleukin-1 (IL-1) and interleukin-6 (IL-6) inhibitors both in clinical trials and in real life. Other inhibitors of these cytokines will be available in the near future, thereby increasing the therapeutic armamentarium. A better understanding of the pathophysiology of sJIA is still needed to identify IL-1 or IL-6 responders, define a potential window of opportunity for early cytokine blockade, and identify a targeted treatment for macrophage activation syndrome. Additional therapeutic targets are needed for a small proportion of patients who do not respond to either IL-1 or IL-6 inhibition.

Keywords: Autoinflammatory disease; IFNγ; IL-1; IL-18; IL-6; Macrophage activation syndrome; Systemic juvenile idiopathic arthritis.