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: 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
• Journal: BMC genomics (BMC Genomics) Vol. 16 Pg. 1076 (Dec 18 2015) ISSN: 1471-2164 [Electronic] England
• PMID: 26679344 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Intercellular Signaling Peptides and Proteins
• Interferon Regulatory Factors
• Interferon Type I
• Receptors, Pattern Recognition

Topics

• Antigen Presentation (immunology)
• Arteritis (diagnosis, etiology)
• Biomarkers
• Case-Control Studies
• Cluster Analysis
• Computational Biology (methods)
• Coronary Artery Disease (diagnosis, etiology)
• Cytokines (metabolism)
• Dendritic Cells (immunology, metabolism)
• Female
• Gene Expression Profiling
• Gene Expression Regulation
• High-Throughput Nucleotide Sequencing
• Humans
• Infant
• Intercellular Signaling Peptides and Proteins (metabolism)
• Interferon Regulatory Factors (genetics)
• Interferon Type I (metabolism)
• Lipid Metabolism (genetics)
• Lymphocyte Activation (genetics, immunology)
• Macrophages (immunology, metabolism)
• Male
• Mucocutaneous Lymph Node Syndrome (complications, diagnosis, therapy)
• Neutrophils (immunology, metabolism)
• Receptors, Pattern Recognition (genetics)
• Signal Transduction
• T-Lymphocyte Subsets (immunology, metabolism)
• Transcriptome