Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in
Tai-Ming Ko1,2,3, Jeng-Sheng Chang4,5, Shih-Ping Chen1
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Insights
Kawasaki disease (KD) involves increased CD177 transcripts and a long non-coding RNA, XLOC_006277. XLOC_006277 is linked to coronary artery aneurysms (CAA) and may play a role in KD pathogenesis.
Area of Science:
- Pediatric Cardiology
- Molecular Biology
- Immunology
Background:
- Kawasaki disease (KD) is a leading cause of acquired pediatric heart disease.
- The specific transcriptomic alterations in KD, particularly those leading to coronary artery aneurysms (CAA), remain poorly understood.
Purpose of the Study:
- To identify key transcripts altered in KD patients.
- To investigate the role of these transcripts in disease progression and CAA development.
Main Methods:
- Blood samples were collected from 37 KD patients across a time-course.
- mRNA and long non-coding RNA (lncRNA) profiling was performed.
- Gene expression levels were analyzed in relation to disease severity and treatment response.
Main Results:
- CD177 transcript levels were elevated in acute KD and in patients resistant to intravenous immunoglobulin (IVIG).
- XLOC_006277, a lncRNA, showed significantly higher expression in acute KD and in patients with CAA.
- XLOC_006277 knockdown reduced the expression of MMP-8 and MMP-9, enzymes implicated in cardiac lesions.
Conclusions:
- Increased CD177-positive neutrophils are associated with KD.
- This study provides a global view of lncRNA profiles in KD, offering insights into CAA pathogenesis.
- XLOC_006277 is a potential biomarker and therapeutic target for KD-associated CAA.
Abstract:
Kawasaki disease (KD) is the most common cause of acquired cardiac disease in children in developed countries. However, little is known regarding the role of transcriptomic targets of KD in the disease progression and development of complications, especially coronary artery aneurysms (CAA). The aim of our study was to identify transcripts affected by KD and their potential role in the disease. We enrolled 37 KD patients and collected blood samples along a comprehensive time-course. mRNA profiling demonstrated an abundance of CD177 transcript in acute KD, and in the intravenous immunoglobulin (IVIG)-resistant group compared to in the IVIG-sensitive group. lncRNA profiling identified XLOC_006277 as the most highly expressed molecule. XLOC_006277 expression in patients at acute stage was 3.3-fold higher relative to patients with convalescent KD. Moreover, XLOC_006277 abundance increased significantly in patients with CAA. XLOC_006277 knockdown suppressed MMP-8 and MMP-9 expression, both associated with heart lesions. Our result suggested that the increase of CD177pos neutrophils was associated with KD. Moreover, this study provided global long non-coding RNA transcripts in the blood of patients with KD, IVIG-resistant KD, or CAA. Notably, XLOC_006277 abundance was associated with CAA, which might contribute to further understanding of CAA pathogenesis in KD.
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