Interleukin-18 and fibroblast growth factor 2 in combination is a useful diagnostic biomarker to distinguish adult-onset Still’s disease from sepsis

OBJECTIVE: To identify potential biomarkers to distinguish adult-onset Still’s disease (AOSD) from sepsis. METHOD: We recruited 70 patients diagnosed with AOSD according to the Yamaguchi criteria, 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the AOSD and sepsis groups in order to identify specific molecular networks. Further, multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by their importance and determine specific biomarkers for distinguishing AOSD from sepsis. RESULTS: Seventeen of the 40 cytokines were found to be suitable for further analyses. The serum levels of eleven were significantly higher in patients with AOSD than healthy controls. Levels of serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and interleukin (IL)-18 were significantly elevated in patients with AOSD compared with those with sepsis, and cytokine clustering patterns differed between these two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both FGF-2 and IL-18 could distinguish AOSD from sepsis with high accuracy (cutoff value for FGF-2 = 36 pg/mL; IL-18 = 543 pg/mL, sensitivity 100%, specificity 72.2%, accuracy 93.8%). CONCLUSION: Determination of FGF-2 and IL-18 levels in combination may represent a biomarker for the differential diagnosis of AOSD from sepsis, based on the measurement of multiple cytokines.