Biomarkers associated with unresponsiveness to IVIG in children with Kawasaki disease

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  • ABE Jun
    Department of Allergy and Immunology, National Research Institute for Child Health and Development
  • MATSUDA Akio
    Department of Allergy and Immunology, National Research Institute for Child Health and Development

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  • 川崎病における治療反応性とバイオマーカー

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We have adopted DNA-microarray technology to analyze gene expression profiles in patients with Kawasaki Disease (KD). The results demonstrated that neutrophils in acute KD patients were not only expanded in number but also activated through the expression of a variety of late-stage granulocyte-specific genes such as polycythemia rubra vera 1 (PRV-1) and haptoglobin compared with febrile controls. In accordance with these findings, serum granulocyte colony-stimulating factor (G-CSF) levels were also higher in IVIG-resistant patients than those in responsive patients. These results might indicate evidences for dysregulated immunological pathways in KD patients and provide possible tools for diagnosis and prognostics of KD. We also found that high-dose IgG specifically and completely inhibited accelerated expression of KD-related cytokines such as G-CSF, IL-6 and IL-1β by HCAEC in response to TNF-α. The suppression of these cytokine genes correlated closely with functional inhibition of a transcription factor, C/EBP-δ. These findings suggest that the clinical effects of IVIG on KD patients are at least in part due to its direct anti-inflammatory effects on the coronary endothelium, which is a major lesion site in the pathogenesis of KD.<br>

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