Abstract
BackgroundKawasaki 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.MethodsDeep 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.ResultsT 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2323-5) contains supplementary material, which is available to authorized users.
Highlights
Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology
Deep RNA sequencing of KD and pediatric control coronary arteries To evaluate the transcriptome of KD arteritis, we compared the RNA expression of KD coronary artery tissues with those of non-inflamed coronary artery tissues from pediatric patients with non-KD illnesses as controls
Heat map analysis of differentially expressed genes in KD and control coronary artery tissues showed that gene expression in KD patients did not cluster by age, time since onset of KD, or treatment, supporting the analysis of the 8 KD tissue
Summary
Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment. Transcriptome profiling of infected tissues, or “dual RNAsequencing” allows for unbiased simultaneous gene expression evaluation of pathogen and host [1]. Kawasaki Disease (KD) is an acute febrile illness of young childhood that can cause medium-sized muscular arteritis, most critically affecting the coronary arteries, and a large body of clinical, epidemiologic, and experimental evidence points to an infectious cause [2, 3]. The purpose of this study was to identify specific cellular pathways and infectious agents in KD coronary arteritis by transcriptome profiling, to elucidate the pathogenesis of the disease. Presented in part at the American Heart Association Annual Meeting November 15–19, 2014, Chicago, IL and at the Eleventh International Kawasaki Disease Symposium, February 3–6, 2015, Honolulu, HI. 1Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-685B, Chicago, IL 60611, USA 2Department of Microbiology and Immunology, Northwestern University
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