Serum biomarkers differentiating Kawasaki disease from febrile infections: A pilot case-control study

Abstract

Although some serum biomarkers are elevated in both Kawasaki disease (KD) and infections, these conditions have not been compared by individual or combined biomarkers. The aim of this study, undertaken between January 2016 and May 2018 in a large teaching hospital, was to compare the serum concentration of cytokines, metalloproteinases (MMP) and heat shock protein (HSP) between cases defined as children with Kawasaki disease (KD) and those with febrile infections (controls) . Serum concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukins (IL 1beta, 6, and 8), heat shock proteins (HSP 60 and 70) and matrix metalloproteinase (MMP 9) were measured on admission in 17 children under six years of age with a temperature >38.5 °C for ≥five days, and compared between the two groups. The median age was 25 months and the median duration of fever eight days. Seven children were diagnosed with KD and ten had a febrile infection. Only the serum concentrations of IL-6 and TNF-alpha were significantly higher in the former than in the latter group ( P = 0.01 and 0.04 respectively). To differentiate between the two groups with the best sensitivity and specificity, the optimal cut-off value for IL-6 was 12.6 pg/mL, and for TNF-alpha 47.9 pg/mL. Their combined increase, however, outperformed their individual concentrations. The characteristic diagnostic “signature” of the combined elevation of IL-6 and TNF-alpha serum levels has the potential, in febrile children, to differentiate early KD from febrile infections, allowing the institution of appropriate therapy.

Serum soluble urokinase plasminogen activator receptor as a biomarker for distinguishing Kawasaki disease from infections in febrile children

“…Their full details were published earlier. 14 There was no significant difference in suPAR concentrations between children with KD (5.35 ± 2.76 ng/mL) and febrile infections (5.57 ± 1.69 ng/mL) (p=0.84) (Fig. 1 Panel A).…”

“…This retrospective observational cohort study is a continuation of an earlier project. 14 It was performed on preserved residual sera from 17 children under six years of age who had fever for ≥ five days and without suggestive diagnostic signs on admission.…”

“…This retrospective observational cohort study is a continuation of an earlier project. 14 It was performed on preserved residual sera from 17 children under six years of age who had fever for ≥ five days and without suggestive diagnostic signs on admission. Plasma samples were collected within 24 hours of admission and were immediately transported to the laboratory for storage at −80°C until further analysis.…”