S100 proteins could not be suppressed by infliximab treatment in refractory Kawasaki disease

  • Kazuyoshi Saito, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Keiichi Hirono, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Yasushi Kemmotsu, The First Department of Pediatrics, Toho University School of Medicine, Japan
  • Keijirou Ibuki, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Hirokazu Kanegane, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Fukiko Ichida, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Tsutomu Saji, The First Department of Pediatrics, Toho University School of Medicine, Japan
  • Toshio Miyawaki, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan

    • Background: Kawasaki disease (KD) is the most common systemic vasculitis syndrome primarily affecting the coronary artery. Infliximab is a monoclonal antibody that binds specifically to human TNF-α-1, and is effective in disorders in which inflammation is mediated by TNF-α. S100 proteins, such as myeloid-related protein (MRP) 8/ MRP14 and S100A12, levels closely correlate with disease activity in acute KD, and potential biomarker to predict coronary artery sequelae in the acute stage of KD.
    Objective: Our aim of study was to treat patients with refractory KD and examine the dynamic changes of S100 proteins during infliximab treatment.
    Methods: We treated 11 KD patients who did not respond to IVIG and/or IVMP with infliximab (5 mg/kg) after median 10 illness days.
    We examined in sequential changes of serum levels of MRP 8/MRP14 and S100A12 before and after infliximab treatment using by ELISA and compared these data with IVIG responders.
    Results: In 8 of 11 patients fever was subsided immediately responded to infliximab treatment. Four patients, who started infliximab after 12 days of illness, developed coronary artery lesions. Each of the cytokines was elevated before infliximab treatment in all patients. Although serum levels of pro-inflammatory cytokines such as IL-6 decreased dramatically after infliximab treatment, MRP8/MRP14 and S100A12 were not suppressed. In contrast, in IVIG responders all cytokines decreased markedly after IVIG treatment.
    Conclusions: Different behaviors of pro-inflammatory cytokines and MRP8/MRP14 and S100A12 after infliximab treatment suggest that infliximab is effective for suppression of cytokine-mediated inflammation, but could not completely block local vasculitis.