title: Ultrastructural, immunofluorescence, and RNA evidence support the hypothesis of a "new" virus associated with Kawasaki disease.
abstract: BACKGROUND
  Intracytoplasmic inclusion bodies (ICI) have been identified in ciliated bronchial epithelium of Kawasaki disease (KD) patients using a synthetic antibody derived from acute KD arterial IgA plasma cells; ICI may derive from the KD etiologic agent.
  
  
  METHODS
  Acute KD bronchial epithelium was subjected to immunofluorescence for ICI and cytokeratin, high-throughput sequencing, and transmission electron microscopy (TEM). Interferon pathway gene expression profiling was performed on KD lung.
  
  
  RESULTS
  An intermediate filament cytokeratin "cage" was not observed around KD ICI, making it unlikely that ICI are overproduced or misfolded human protein aggregates. Many interferon-stimulated genes were detected in the bronchial epithelium, and significant modulation of the interferon response pathway was observed in the lung tissue of KD patients. No known virus was identified by sequencing. Aggregates of virus-like particles (VLP) were detected by TEM in all 3 acute KD patients from whom nonembedded formalin-fixed lung tissue was available.
  
  
  CONCLUSIONS
  KD ICI are most likely virus induced; bronchial cells with ICI contain VLP that share morphologic features among several different RNA viral families. Expedited autopsies and tissue fixation from acute KD fatalities are urgently needed to more clearly ascertain the VLP. These findings are compatible with the hypothesis that the infectious etiologic agent of KD may be a "new" RNA virus.
authors.affiliation: Department of Pediatrics, Feinberg School of Medicine, Children's Memorial Hospital, Northwestern University, Chicago, Illinois 60611, USA. a-rowley@northwestern.edu
authors.forename: Anne H
authors.initials: AH
authors.lastname: Rowley
authors.forename: Susan C
authors.initials: SC
authors.lastname: Baker
authors.forename: Stanford T
authors.initials: ST
authors.lastname: Shulman
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Rand
authors.forename: Maria S
authors.initials: MS
authors.lastname: Tretiakova
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Garcia
authors.forename: Nuzhath F
authors.initials: NF
authors.lastname: Tajuddin
authors.forename: Linda M
authors.initials: LM
authors.lastname: Fox
authors.forename: Julia H
authors.initials: JH
authors.lastname: Huang
authors.forename: J Carter
authors.initials: JC
authors.lastname: Ralphe
authors.forename: Kei
authors.initials: K
authors.lastname: Takahashi
authors.forename: Jared
authors.initials: J
authors.lastname: Flatow
authors.forename: Simon
authors.initials: S
authors.lastname: Lin
authors.forename: Mitra B
authors.initials: MB
authors.lastname: Kalelkar
authors.forename: Benjamin
authors.initials: B
authors.lastname: Soriano
authors.forename: Jan M
authors.initials: JM
authors.lastname: Orenstein
mesh_terms: D002675:Child, Preschool; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007181:Inclusion Bodies, Viral / Q000473:pathology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D046529:Microscopy, Electron, Transmission; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020545:Respiratory Mucosa / Q000821:virology; D022701:Virosomes / Q000276:immunology / Q000648:ultrastructure; D014780:Viruses / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity* / Q000648:ultrastructure
chemical_list: D012367:RNA, Viral; D022701:Virosomes