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BMC Pediatrics
Published in: BMC Pediatrics 1/2024

Open Access 01-12-2024 | Kawasaki Disease | Research

NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study

Authors: Beirong Yu, Bangxu Zheng, Yu Shen, Yijing Shen, Haiyan Qiu, Ling Wu, Yuanling Chen, Xiaohong Cai, Junhua Wu, Qingxiao Hong

Published in: BMC Pediatrics | Issue 1/2024

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Abstract

Background

Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD.

Methods

In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated.

Results

Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762–0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value.

Conclusions

Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.
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Metadata
Title
NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study
Authors
Beirong Yu
Bangxu Zheng
Yu Shen
Yijing Shen
Haiyan Qiu
Ling Wu
Yuanling Chen
Xiaohong Cai
Junhua Wu
Qingxiao Hong
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2024
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-024-04672-8

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