CXCL10/IP-10 is a Biomarker and Mediator for Kawasaki Disease
Rationale: Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult.
Objective: To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD.
Methods and Results: We enrolled 214 children with fever and clinical features suggestive of KD. Of those, only 100 were diagnosed with KD. Their plasma samples were globally analyzed for cytokines, chemokines, and cell adhesion molecules using an unbiased, large-scale, quantitative protein array. This study was conducted in 3 stages: discovery, replication, and blinded validation. During the discovery phase [n(KD)=37, n(control)=20], the expression of interleukin-17F, sCD40L, E-selectin, CCL23(MPIF-1), and CXCL10(IP-10) were upregulated during the acute phase in KD patients compared to that in the controls. A notable increase was observed in the IP-10 levels (KD, 3,037±226.7 pg/mL; control, 672±130.4 pg/mL; p =4.1 × 10-11). Receiver-operating characteristic analysis of the combined discovery and replication data [n(KD)=77, n(control)=77] showed that the IP-10 level had high area under the curve values (0.94 [95% confidence interval, 0.9055-0.9778]; sensitivity, 100%; and specificity, 77%). With 1,318 pg/mL as the optimal cut-off, the blinded validation study confirmed that the IP-10 levels were a good predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the T cells of acute KD patients.
Conclusions: IP-10 may be used as a biomarker to facilitate KD diagnosis, and it may provide clues about the pathogenesis of KD.
- Received December 29, 2014.
- Revision received January 13, 2015.
- Accepted January 20, 2015.