title: Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease.
abstract: BACKGROUND
  Global gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD.
  
  
  METHODS
  To gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes.
  
  
  RESULTS
  The overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target.
  
  
  CONCLUSIONS
  Our study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.
authors.affiliation: Genome Institute of Singapore, Singapore City, Singapore.
authors.forename: Long Truong
authors.initials: LT
authors.lastname: Hoang
authors.affiliation: Department of Pediatrics, University of California San Diego and Rady Children's Hospital, La Jolla, CA 92093 USA.
authors.forename: Chisato
authors.initials: C
authors.lastname: Shimizu
authors.affiliation: Genome Institute of Singapore, Singapore City, Singapore.
authors.forename: Ling
authors.initials: L
authors.lastname: Ling
authors.affiliation: Genome Institute of Singapore, Singapore City, Singapore.
authors.forename: Ahmad Nazri Mohamed
authors.initials: AN
authors.lastname: Naim
authors.affiliation: Genome Institute of Singapore, Singapore City, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Department of Pediatrics, University of California San Diego and Rady Children's Hospital, La Jolla, CA 92093 USA.
authors.forename: Adriana H
authors.initials: AH
authors.lastname: Tremoulet
authors.affiliation: Section for Pediatrics, Division of Medicine, Imperial College, London, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Wright
authors.affiliation: Section for Pediatrics, Division of Medicine, Imperial College, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.affiliation: Genome Institute of Singapore, Singapore City, Singapore.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.affiliation: Department of Pediatrics, University of California San Diego and Rady Children's Hospital, La Jolla, CA 92093 USA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Burns