Abstract
INTRODUCTIONKawasaki disease (KD) is a type of childhood febrile systemic vasculitis. Inflammasomes control inflammatory signaling and are related with the development of KD. In this study, we performed a survey of transcripts and global DNA methylation levels of inflammasome sensors of NOD-like receptors (NLRs) and the downstream interleukin 1β (IL-1β).MATERIALS AND METHODSIn this study, for the chip studies, we recruited a total of 18 KD patients, who we analyzed before receiving intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, as well as 36 non-fever controls by Illumina HumanMethylation 450 BeadChip and Affymetrix GeneChip® Human Transcriptome Array 2.0. A separate group of 78 subjects was performed for real-time quantitative PCR validations.RESULTSThe expressions of mRNA levels of NLRC4, NLRP12, and IL-1β were significantly upregulated in KD patients compared to the controls (p<0.05). Once KD patients underwent IVIG treatment, these genes considerably decreased. In particular, the methylation status of the CpG sites of these genes indicated a significant opposite tendency between the KD patients and the controls. Furthermore, mRNA levels of IL-1β represented a positive correlation with NLRC4 (p=0.002). We also observed that the mRNA levels of NLRP12 were lower in KD patients who developed coronary arterial lesions (p<0.005).CONCLUSIONThis study is among the first to report epigenetic hypomethylation, increased transcripts, and the upregulation of NLRC4, NLRP12 and IL-1β in KD patients. Moreover, a decreased upregulation of NLRP12 was related to coronary arterial lesion formation in KD patients.
Highlights
Kawasaki disease (KD) is a type of childhood febrile systemic vasculitis
The expressions of mRNA levels of NLRC4, NLRP12, and interleukin 1β (IL-1β) were significantly upregulated in KD patients compared to the controls (p
IL-1β expression levels positively correlate with NLRC4, while NLRP12 was lower in KD patients who developed coronary artery lesions (CALs) than those who did not
Summary
Kawasaki disease (KD) is a type of childhood febrile systemic vasculitis. Inflammasomes control inflammatory signaling and are related with the development of KD. KD’s most serious cardiovascular complications are caused by coronary artery lesions (CALs) and include coronary artery fistula formations [2], arterial remodeling, and coronary artery aneurysms (CAAs) [3] This disease can be treated, nearly 20% of children who do not receive treatment suffer a CAA [2], which, in severe cases, may even cause death. Toll-like receptors (TLRs) function as the sensor arm of the innate immune system and induce proinflammatory cytokine expressions [4]. Researchers have strongly suggested that autoinflammatory diseases are disorders of the innate immune system, are characterized by systemic inflammation often caused by inflammasomes, and are free from infection and autoreactive antibodies or antigen-specific T cells [8]. Several clinical and experimental animal models have strongly implicated the function of IL-1β in KD [11,12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
