Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

Huang, Ying‐Hsien; Li, Sung‐Chou; Huang, Lien‐Hung; Chen, Pao-Chun; Lin, Yun-Huin; Lin, Chih-Chien; Kuo, Ho-Chang

doi:10.18632/oncotarget.14497

Cited by 44 publications

(81 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the exact etiology of KD remains uncertain, we have reported that KD stimulates the extraordinary upregulation of TLR1, 2, 4, 5, 6, and 9, which correlates with bacteria-related pathogen-associated molecular patterns, except for the activation of TLR3 and 7, which relates to double-stranded RNA and single-stranded viral RNA in the acute stage of KD. [8]. This study’s results support the idea that KD induces a bacterium-like inflammatory disease.…”

Section: Kawasaki Disease: the Most Common Acute Coronary Vasculitsupporting

confidence: 84%

Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker

Huang

Kuo

2017

IJMS

Self Cite

View full text Add to dashboard Cite

Kawasaki disease (KD) is an autoimmune-like disease and acute childhood vasculitis syndrome that affects various systems but has unknown etiology. In addition to the standard diagnostic criteria, anemia is among the most common clinical features of KD patients and is thought to have a more prolonged duration of active inflammation. In 2001, the discovery of a liver-derived peptide hormone known as hepcidin began revolutionizing our understanding of anemia’s relation to a number of inflammatory diseases, including KD. This review focuses on hepcidin-induced iron deficiency’s relation to transient hyposideremia, anemia, and disease outcomes in KD patients, and goes on to suggest possible routes of further study.

show abstract

Section: Kawasaki Disease: the Most Common Acute Coronary Vasculitsupporting

confidence: 84%

Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker

Huang

Kuo

2017

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Regarding the implication of PRRs, Huang et al (100) reported that the CpG sites of TLR genes were reversibly hypomethylated in the peripheral whole blood cells of acute KD patients, resulting in upregulated expression of TLRs. This transient epigenetic change supposedly potentiates the TLR-dependent innate immune response.…”

Section: Other Insight To Pamps/mamps Hypothesis In Kdmentioning

confidence: 99%

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

2019

View full text Add to dashboard Cite

Kawasaki disease (KD) is a pediatric vasculitis syndrome that is often involves coronary artery lesions (e. g., coronary artery aneurysms). Although its causal factors and entire pathogenesis remain elusive, the available evidence indicates that the pathogenesis of KD is closely associated with dysregulation of immune responses to various viruses or microbes. In this short review, we address several essential aspects of the etiology of KD with respect to the immune response to infectious stimuli: 1) the role of viral infections, 2) the role of bacterial infections and the superantigen hypothesis, 3) involvement of innate immune response including pathogens/microbe-associated molecular patterns and complement pathways, and 4) the influence of genetic background on the response to infectious stimuli. Based on the clinical and experimental evidence, we discuss the possibility that a wide range of microbes and viruses could cause KD through common and distinct immune processes.

show abstract

“…We have previously reported that IVIG administration significantly affects methylation pattern alterations in KD patients [17][18][19]. In short, DNA methylation can affect an inactive gene through DNA methyltransferases [20].…”

Section: Introductionmentioning

confidence: 99%

HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

Huang

Kuo

et al. 2018

Journal of Molecular and Cellular Cardiology

Self Cite

View full text Add to dashboard Cite

Kawasaki disease (KD) is the most common coronary vasculitis to appear in children with anemia and has been associated with elevated plasma hepcidin levels. We recruited a total of 241 cases, including 18 KD patients, who were tested both prior to receiving intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, and 18 febrile controls, who were observed in the Illumina HumanMethylation450 BeadChip study for their CpG markers. The remaining cases consisted of another 92 KD patients and 113 controls that were used for validation by pyrosequencing. We performed a genetic functional study using Luciferase assays. A support vector machine (SVM) classification model was adopted to identify KD patients and control subjects. In this study, KD patients clearly demonstrated a significantly epigenetic hypomethylation of HAMP promoter compared to controls. After receiving IVIG treatment, the hypomethylation status in KD patients was restored, and we observed a significant opposite tendency between the DNA methylation of target CpG sites (cg23677000 and cg04085447) and the hepcidin level. Furthermore, reporter gene assays were used to detect target CpG sites, the methylation of which displayed decreased levels of HAMP gene expression. Of particular note, we developed a SVM classification model with a 90.9% sensitivity, a 91.9% specificity, and 0.94 auROC in the training set. An independent blind cohort also had good performance (96.1% sensitivity and 89.7% specificity). In this study, we demonstrate HAMP promoter hypomethylation, which upregulates hepcidin expression in KD patients. Furthermore, the reliability and robustness of our SVM classification model can accurately serve as KD biomarkers.

show abstract

Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

Cited by 44 publications

References 34 publications

Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker

Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

Contact Info

Product

Resources

About