title: The transcriptional profile of coronary arteritis in Kawasaki disease.
abstract: BACKGROUND
  Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.
  
  
  METHODS
  Deep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD.
  
  
  RESULTS
  T lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis.
  
  
  CONCLUSIONS
  The immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies.
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-685B, Chicago, IL, 60611, USA. a-rowley@northwestern.edu.|Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. a-rowley@northwestern.edu.|Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. a-rowley@northwestern.edu.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Rowley
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, USA.|The McDonnell Genome Institute at Washington University, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Wylie
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Kwang-Youn A
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-685B, Chicago, IL, 60611, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Pink
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-685B, Chicago, IL, 60611, USA.|Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.|Present address: AbbVie, Inc, North Chicago, IL, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Reindel
authors.affiliation: Department of Microbiology/Immunology, Loyola University Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Baker
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-685B, Chicago, IL, 60611, USA.|Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: Stanford T
authors.initials: ST
authors.lastname: Shulman
authors.affiliation: Department of Pathology, George Washington University School of Medicine, Washington, DC, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Orenstein
authors.affiliation: Department of Pathology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.affiliation: The McDonnell Genome Institute at Washington University, Washington University School of Medicine, Saint Louis, MO, USA.|Present address: The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, USA.|The McDonnell Genome Institute at Washington University, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Todd N
authors.initials: TN
authors.lastname: Wylie
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D001167:Arteritis / Q000175:diagnosis / Q000209:etiology*; D015415:Biomarkers; D016022:Case-Control Studies; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics; D007370:Interferon Type I / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D051192:Receptors, Pattern Recognition