Human Transcriptome Array Analysis Identifies CDR2 as a Novel Suppressed Gene for Kawasaki Disease
Ying-Hsien Huang1,2, Kuang-Den Chen1,3, Kuang-Che Kuo1,2
1Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Insights
This study identified novel suppressed genes in Kawasaki disease (KD), including CDR2 and DDX24. These findings offer potential new insights into KD pathogenesis and the development of coronary artery lesions (CAL).
Area of Science:
- Pediatric Rheumatology
- Immunology
- Genetics
Background:
- Kawasaki disease (KD) is a critical childhood vasculitis affecting coronary arteries.
- Previous research primarily focused on activated genes during the acute phase of KD.
- Understanding suppressed genes offers new avenues for KD research and potential prognostic markers.
Purpose of the Study:
- To identify suppressed genes in the acute stage of Kawasaki disease.
- To investigate the clinical significance and prognostic value of these suppressed genes.
- To explore the role of specific genes, like DDX24, in the development of coronary artery lesions (CAL).
Main Methods:
- Human transcriptome array (HTA) 2.0 analysis was performed on patients with KD, healthy controls (HC), and febrile controls (FC).
- Gene expression was validated using quantitative reverse transcription PCR (qRT-PCR).
- Analysis included 18 KD patients and 18 HC for HTA, and 31 KD patients and 39 controls for qRT-PCR.
Main Results:
- HTA 2.0 identified 461 upregulated and 99 suppressed genes in KD patients.
- BCL11B, DUSP2, DDX24, and CDR2 were the most downregulated genes, with expression increasing after IVIG treatment.
- CDR2 mRNA expression correlated well with HTA 2.0 results, and higher DDX24 mRNA was observed in KD patients with CAL post-IVIG.
Conclusions:
- This study highlights novel suppressed genes, particularly CDR2, in Kawasaki disease.
- DDX24 gene expression is associated with the formation of coronary artery lesions (CAL) in KD patients.
- These findings contribute to a deeper understanding of KD pathogenesis and may offer prognostic value.
Abstract:
Kawasaki disease (KD) is a febrile childhood vasculitis that involves the coronary arteries. Most previous studies have focused on the genes activated in the acute phase of KD. However, in this study, we focused on suppressed genes in the acute stage of KD and identified novel targets with clinical significance and potential prognostic value for KD patients. We enrolled 18 patients with KD, 18 healthy controls (HC), and 18 febrile controls (FC) for human transcriptome array analysis. Another 19 healthy controls, 20 febrile controls, and 31 patients with KD were recruited for RT-PCR validation of target mRNA expressions. The results of Human Transcriptome Array (HTA) 2.0 showed 461 genes that were significantly higher in KD and then normalized after IVIG, as well as 99 suppressed genes in KD. Furthermore, we identified the four genes in KD with the most downregulation, including BCL11B, DUSP2, DDX24, and CDR2, as well as the upregulation of their expression following IVIG administration. The mRNA expression of CDR2 by qRT-PCR was the most compatible with the pattern of the HTA2.0 results. Furthermore, we found higher DDX24 mRNA expression in KD patients with CAL when compared to those without CAL 3 weeks after IVIG administration. In summary, activated gene expression represented a majority in the immune response of KD. In this study, we identified CDR2 as a novel suppressed gene for Kawasaki disease via human transcriptome array analysis and DDX24 associated with CAL formation, which may contribute to further understanding of CAL pathogenesis in KD.
