Neutrophil Extracellular Traps Formation and Citrullinated Histones 3 Levels in Patients with Kawasaki Disease
Jing Hu1, Wei Qian1, Tianhe Wang1
1Wuxi Children's Hospital Affiliated, Jiangnan University, China.
Insights
Kawasaki disease (KD) involves increased neutrophil extracellular traps (NETs) and citrullinated histone 3 (H3Cit) in acute phases. Intravenous immunoglobulin (IVIG) treatment effectively reduced these markers in KD patients.
Area of Science:
- Immunology
- Pediatric Rheumatology
- Vascular Biology
Background:
- Kawasaki disease (KD) is an autoimmune vasculitis linked to vascular injury.
- Neutrophil extracellular traps (NETs), composed of proteins like citrullinated histone 3 (H3Cit), are implicated in inflammatory processes.
- The role of NETs and H3Cit in KD pathogenesis was previously unknown.
Purpose of the Study:
- To investigate the levels of NETs and H3Cit in children diagnosed with Kawasaki disease.
- To assess the impact of disease phase and intravenous immunoglobulin (IVIG) treatment on NETs and H3Cit levels.
Main Methods:
- Children with KD were categorized into acute and sub-acute phases, with or without IVIG treatment.
- Peripheral blood samples were analyzed for NETs using flow cytometry.
- H3Cit levels were quantified using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Acute KD demonstrated significantly elevated NETs counts compared to healthy controls.
- H3Cit levels were markedly higher in the acute KD group versus healthy controls.
- IVIG treatment led to a significant reduction in both NETs and H3Cit levels in KD patients.
Conclusions:
- Acute Kawasaki disease is associated with heightened NETs formation and elevated H3Cit levels.
- Intravenous immunoglobulin therapy effectively suppresses NETs production and lowers plasma H3Cit in KD patients.
- These findings highlight NETs and H3Cit as potential biomarkers and therapeutic targets in Kawasaki disease.
Background:
Kawasaki disease (KD) is a vasculitis associated with vascular injury and autoimmune response. Inflammatory factors stimulate neutrophils to produce web-like structures called neutrophil extracellular traps (NETs). Citrullinated histone 3 (H3Cit) is one of the main protein components of neutrophil extracellular traps involved in the process of NETosis. The levels of NETs and H3Cit in the KD are not known.
Objective:
To determine the changes in the levels of NETs and H3Cit in KD.
Methods:
Children with KD were recruited and divided into the acute KD and the sub-acute KD group according to the disease phase and whether intravenous immunoglobulin (IVIG) was used or not. Peripheral venous blood was taken before and after the IVIG administration and sent for the examination of NETs by flow cytometry. The level of H3Cit was measured by enzyme-linked immunosorbent assay (ELISA).
Results:
The counts of NETs in the acute KD group significantly increased compared with the healthy controls (p<0.01). The level of H3Cit was significantly higher in the acute KD group than in the healthy control subjects. Of note, both the counts of NETs and the level of H3Cit decreased in the KD patients treated with IVIG compared with the acute KD group (p<0.01).
Conclusion:
Acute KD is characterized by an increased formation of NETs and high levels of H3Cit. IVIG significantly inhibited NETs formation and also reduced the level of plasma H3Cit in children with KD.
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