Background
Kawasaki disease (KD) is a systemic vasculitis of young children. Currently, one third of all cases do not meet all the currently used clinical criteria for diagnosis, which is a serious issue since >25% of untreated patients develop coronary artery abnormalities such as aneurysms. These issues are compounded because other inflammatory diseases including viral infection, toxin-mediated diseases and the rare pediatric COVID-19 related condition, MIS-C, display many KD symptoms.
A group from Boston Children’s Hospital have addressed this problem by using the Olink® Target 48 Cytokine panel to look for circulating proteins that can diagnose KD and discriminate it from other pediatric febrile/inflammatory conditions. Plasma proteins were compared in healthy pediatric controls, febrile controls presenting with 3 days’ fever but no clinical signs of KD, and patients with KD, MIS-C, macrophage activation syndrome, systemic- and non-systemic juvenile idiopathic arthritis, or juvenile dermatomyositis. Key findings were then validated using serum samples from additional patients with KD and febrile controls.
Outcome
Increased levels of many proinflammatory mediators were found in patients with KD, MIS-C and other febrile conditions compared to controls. Within the multiple groups of inflammatory disease, increased IL-17A, IL-17C, IL-17F, IL-13, and CCL13 discriminated KD from the others. The increase in IL-17A compared to controls was confirmed using an ELISA, with strong correlation between the two methods.
Pairwise comparison of KD vs MIS-C & febrile controls revealed 21 markers elevated in KD, and validation using a separate cohort replicated 18 of these. The utility of IL-17A, IL-17C, and IL-17F as diagnostic biomarkers of KD was then examined. IL-17A showed the best diagnostic performance, with with an Area Under the Curve, AUC=0.95. IL-17 cytokines also showed minimal correlation with C-reactive protein (CRP), indicating that they are not simply surrogate markers of systemic inflammation in KD. The IL-17 proteins were also examined in terms of development of complications from coronary artery aneurysms (CAA) and in all but one of 20 patients with CAA, all three IL-17 family members showed elevated levels.
The authors concluded that elevation of IL-17 family cytokines is a hallmark of KD and may help to distinguish KD from its clinical mimics.
