Fig. 2

Identified biomarkers grouped by clinical question. a Diagnostic biomarkers are shown that differentiated systemic juvenile idiopathic arthritis (SJIA) from healthy controls (HC) or other non-JIA disease (D1), SJIA vs other JIA subtypes (D2) or both (D1 and D2). b Prognostic biomarkers for flare (P1), increased disease activity or discriminating active disease from inactive (P2), for macrophage activation syndrome (MAS) or discriminating MAS from SJIA flare (P3), or a combination of these are shown. The specific clinical question is very important in interpreting the results of biomarker studies. Little overlap between different diagnostic questions suggests a predominance of different pathways during different stages of disease and therefore a specific hypothesis and clinical question is more useful in studies to understand mechanisms. Biomarkers that are broad enough to cover more than one diagnostic or prognostic category may be more likely to have a specific role in the underlying immunological pathology, and as broad markers will be more useful for wider clinical care. By performing this analysis we can create a shortlist of biomarkers on which to focus. Indeed, only a few markers fall into this group, but perhaps they should receive most attention for future validation in preference to other markers. ACAN aggrecan core protein cartilage-specific core protein, ACCP anti-cyclic citrullinated peptide, ACPA anti-citrullinated protein antibodies, ACT alpha-1-antichymotrypsin, AECA anti-endothelial cell antibodies, ANA antinuclear antibodies, Anti-BiP anti-immunoglobulin binding protein/glucose regulated protein 78 (GRP78), APO apolioprotein, APRIL A proliferation-inducing ligand, B2M Beta -2-microglobulin, BAFF B-cell activating factor, COMP cartilage oligomeric matrix protein, CRP C-reactive protein, FSTL-1 follistatin-like protein 1, GSN Gelsolin, HO-1 heme oxygenase-1, IFN interferon, IL-18BP IL-18 binding protein, LGAL galectin, MMP matrix metalloproteinase, ONP osteopontin, SAA serum amyloid A, SAP serum amyloid P, sICAM-1 soluble intracellular adhesion molecule-1, sST2 soluble ST2/IL-1 receptor-like 1, TIMP tissue inhibitors of metalloproteinase, TTr transthyretin