The transcriptional profile of coronary arteritis in Kawasaki disease

Anne H. Rowley*, Kristine M. Wylie, Kwang Youn A. Kim, Adam J. Pink, Amy Yang, Rebecca Reindel, Susan C. Baker, Stanford T. Shulman, Jan M. Orenstein, Mark W. Lingen, George M. Weinstock, Todd N. Wylie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 aα 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.

Original languageEnglish (US)
Article number1076
JournalBMC Genomics
Volume16
Issue number1
DOIs
StatePublished - Dec 18 2015

Keywords

  • Acquired immune response
  • Arteritis
  • Childhood
  • Coronary artery aneurysm
  • Innate immune response
  • Kawasaki disease

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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