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Published on: January 28, 2020
The transcriptional profile of coronary arteritis in Kawasaki disease
Anne H Rowley1,2,3, Kristine M Wylie4,5, Kwang-Youn A Kim6
1Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-685B, Chicago, IL, 60611, USA. a-rowley@northwestern.edu.
Insights
Kawasaki disease (KD) coronary arteries show an antiviral immune response, with upregulated T cell activation and interferon pathways. This finding offers insights into KD pathogenesis and potential new treatments.
Area of Science:
- Cardiovascular Research
- Immunology
- Pediatric Infectious Diseases
Background:
- Kawasaki disease (KD) is a serious childhood illness causing coronary arteritis with a suspected infectious origin.
- Understanding the gene expression in affected tissues is crucial for diagnosing and treating KD.
- RNA sequencing offers a powerful method to explore the host response in KD.
Purpose of the Study:
- To investigate the gene expression profile in coronary artery tissues of children with Kawasaki disease.
- To identify potential etiological factors and host responses contributing to KD pathogenesis.
- To explore new diagnostic and therapeutic strategies for KD.
Main Methods:
- Deep RNA sequencing was performed on coronary artery tissues from 8 KD patients and 7 healthy children.
- Bioinformatics analysis identified 1074 differentially expressed messenger RNAs (mRNAs).
- Microbial sequences were analyzed for association with KD using a specialized platform and Metastats.
Main Results:
- Significant upregulation of T lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response in KD arteritis.
- No differential expression was observed in the tumor necrosis factor α pathway.
- No specific association was found between transcripts of known infectious agents and KD coronary arteritis.
Conclusions:
- The immune transcriptional profile in KD coronary arteries exhibits characteristics of an antiviral response.
- Upregulation of cytotoxic T lymphocyte and type I interferon-induced genes suggests a specific host response in KD.
- These findings can inform the development of novel immunomodulatory therapies for high-risk KD patients and guide future etiological research.
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.
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