Abstract
Systemic onset Juvenile Idiopathic Artritis (sJIA) is considered to be an autoinflammatory disease. The S100-proteins S100A8, S100A9 and S100A12 in serum and interleukin (IL)-18 in plasma are extremely elevated in sJIA patients and have been proposed to be useful biomarkers for diagnosis, disease activity and response to therapy. Moreover, sJIA patients seem to have a defective IL-18 NK cell axis as NK cell lytic function is impaired in spite of high IL-18 levels. However, it is still unknown how the inflammatory S100 proteins and IL-18 relate to each other, and to the defective NK cell lytic function.
Highlights
Systemic onset Juvenile Idiopathic Artritis is considered to be an autoinflammatory disease
Stimulation of Peripheral blood mononuclear cells (PBMCs) with S100A8, S100A9 and S100A12 resulted in cytokine production of IL-1b, IL-18 as well as IL-6 and TNF-a
Blocking TLR4 by adding CLI-095 decreased cytokine production to near normal levels, while blocking RAGE did not have an effect on cytokine production
Summary
Systemic onset Juvenile Idiopathic Artritis (sJIA) is considered to be an autoinflammatory disease. The S100-proteins S100A8, S100A9 and S100A12 in serum and interleukin (IL)-18 in plasma are extremely elevated in sJIA patients and have been proposed to be useful biomarkers for diagnosis, disease activity and response to therapy. SJIA patients seem to have a defective IL-18 NK cell axis as NK cell lytic function is impaired in spite of high IL-18 levels. It is still unknown how the inflammatory S100 proteins and IL-18 relate to each other, and to the defective NK cell lytic function
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