title: New developments in the search for the etiologic agent of Kawasaki disease.
abstract: OBJECTIVE
  The aim of this article is to review recent developments in the search for the etiologic agent of Kawasaki disease.
  
  
  RESULTS
  Two recently proposed theories of Kawasaki disease etiology, the toxic shock syndrome toxin-1 hypothesis and the coronavirus NL-63 hypothesis, have been studied extensively and have been disproven. Surprisingly, IgA plasma cells infiltrate inflamed tissues in acute Kawasaki disease, including the coronary artery, and are oligoclonal, or antigen-driven. Synthetic versions of predominant IgA antibodies in acute Kawasaki disease arterial tissue bind to an antigen present in acute Kawasaki disease ciliated bronchial epithelium and in a subset of macrophages in acute inflamed Kawasaki disease tissues. Light and electron microscopic studies of the antigen in acute Kawasaki disease ciliated bronchial epithelium indicate that the Kawasaki disease-associated antigen localizes to cytoplasmic inclusion bodies that are consistent with aggregates of viral protein and associated nucleic acid.
  
  
  CONCLUSIONS
  The identification of cytoplasmic inclusion bodies in acute Kawasaki disease ciliated bronchial epithelium has provided direction for future Kawasaki disease etiology studies. Transmission electron microscopic examination of glutaraldehyde-fixed medium-sized bronchi from acute Kawasaki disease fatalities and analysis of the protein and nucleic acid components of the inclusions should provide important information about these inclusion bodies and speed the identification of the specific etiologic agent of Kawasaki disease.
authors.affiliation: Northwestern University Feinberg School of Medicine, The Children's Memorial Hospital, Chicago, Illinois 60601, USA. a-rowley@northwestern.edu
authors.forename: Anne H
authors.initials: AH
authors.lastname: Rowley
authors.forename: Stanford T
authors.initials: ST
authors.lastname: Shulman
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis / Q000235:genetics; D001980:Bronchi / Q000276:immunology* / Q000648:ultrastructure; D017934:Coronavirus / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000235:genetics; D002479:Inclusion Bodies / Q000276:immunology; D009080:Mucocutaneous Lymph Node Syndrome / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D009687:Nuclear Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D007070:Immunoglobulin A; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014157:Transcription Factors; C493987:SPMIP6 protein, human; C114928:toxic shock syndrome toxin 1 (101-158)