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Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis; a cross-sectional study
  1. Wilco de Jager (wjager{at}
  1. University Medical Center Utrecht, Netherlands
    1. Esther PAH Hoppenreijs (e.hoppenreijs{at}
    1. University Medical Center Nijmegen, Netherlands
      1. Nico M Wulffraat (n.wulffraat{at}
      1. University Medical Center Utrecht, Netherlands
        1. Lucy R Wedderburn (l.wedderburn{at}
        1. Institute of Child Health, University College London, United Kingdom
          1. Wietse Kuis (wkuis{at}
          1. University Medical Center Utrecht, Netherlands
            1. Berent J Prakken (bprakken{at}
            1. University Medical Center Utrecht, Netherlands


              Juvenile idiopathic arthritis (JIA) consists of a heterogeneous group of disorders with, for the most part, an unknown immunopathogenesis. Although onset and disease course differ, the subtypes of JIA share the occurrence of chronic inflammation of the joints, with infiltrations of immune competent cells that secrete inflammatory mediators. We undertook the present study to identify a panel of cytokines that is specifically related to the inflammatory process in JIA. Using a novel technology, the multiplex immunoassay we measured 30 cytokines in plasma from 65 JIA patients, of which 34 were paired with synovial fluid. We compared these data with plasma of 20 healthy controls and 9 patients with type I diabetes, a chronic inflammatory disease. JIA patients have, irrespective of their subclassification, significant higher levels of TNFa, MIF, CCL2, CCL3, CCL11, CCL22 and CXCL9 in plasma compared with healthy controls. In paired plasma and synovial fluid samples of JIA patients significant higher levels IL6, IL15, CCL2, CCL3, CXCL8, CXCL9 and CXCL10 are present in synovial fluid. Cluster analysis within all JIA patients reveals a pre dominant pro inflammatory cytokine cluster during active disease whereas a regulatory / anti-inflammatory related cytokine cluster is observed during remission. Furthermore we tested if a discrimination profile of various cytokines could be helpful in determination of disease classification. We suggest several cytokines (IL18, MIF, CCL2, CCL3, CCL11, CXCL9 and CXCL10) may correspond to the activation status during inflammation in JIA and could be instrumental to monitor disease activity, and therapy outcome of (new) immuno-therapies.

              • cytokines
              • juvenile idiopathic arthritis
              • luminex

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                BMJ Publishing Group Ltd and European League Against Rheumatism