Related Experiment Video
Updated: Jun 30, 2025
Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase G6PI-Induced RA Mice
Published on: January 31, 2020
NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study
Beirong Yu1, Bangxu Zheng2, Yu Shen1
1Department of Pediatrics, Ningbo Women and Children's Hospital, Ningbo, Zhejiang, China.
Insights
NLR Family CARD Domain Containing 4 (NLRC4) promoter hypomethylation is a potential biomarker for Kawasaki disease (KD) diagnosis and treatment monitoring. This epigenetic change in KD patients reverses with intravenous immunoglobulin (IVIG) therapy.
Area of Science:
- Epigenetics
- Immunology
- Pediatric Medicine
Background:
- Kawasaki disease (KD) is a critical systemic vasculitis impacting children, necessitating better diagnostic and therapeutic strategies.
- Understanding the molecular underpinnings of KD is vital for improved patient outcomes.
- NLR Family CARD Domain Containing 4 (NLRC4) is a key inflammasome component involved in immune responses.
Purpose of the Study:
- To investigate the potential of NLRC4 promoter methylation as a diagnostic biomarker for Kawasaki disease.
- To explore the association between NLRC4 methylation and disease activity or treatment response in KD.
Main Methods:
- Pyrosequencing analysis of NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 healthy controls.
- Evaluation of methylation at five specific CpG sites within the NLRC4 promoter region.
- Receiver Operating Characteristic (ROC) curve analysis to assess diagnostic accuracy.
Main Results:
- Significantly decreased NLRC4 promoter methylation was observed in KD patients compared to controls across all evaluated CpG sites and average methylation.
- NLRC4 methylation levels showed significant reversal following intravenous immunoglobulin (IVIG) treatment.
- Mean NLRC4 gene methylation demonstrated strong diagnostic capability for KD (AUC=0.844).
- NLRC4 promoter methylation correlated negatively with granulocyte percentage, age, hemoglobin, and erythrocyte volume, and positively with lymphocyte percentage and absolute lymphocyte count.
Conclusions:
- Peripheral NLRC4 hypomethylation plays a role in Kawasaki disease pathogenesis and response to IVIG treatment.
- NLRC4 methylation could serve as a potential biomarker for monitoring KD treatment.
- Further research is needed to fully elucidate the precise functions of NLRC4 methylation in KD.
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.
More Related Videos
11:06Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
Published on: September 20, 2017
09:43Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022