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Kawasaki disease-specific molecules in the sera are linked to microbe-associated molecular patterns in the biofilms
Takeshi Kusuda1, Yasutaka Nakashima1, Kenji Murata1
1Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background:
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis.
Methods:
We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum samples from 117 patients with KD and 106 controls. Microbiological and LC-MS evaluation of biofilm samples were also performed.
Results:
KD samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (common MAMPs from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus) at the 1st study period, and from the biofilms formed in vivo (common MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus) at the 2nd and 3rd periods. The biofilm extracts from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus also induced proinflammatory cytokines by HCAECs. By the experiments with IgG affinity chromatography, some of these serum KD-specific molecules bound to IgG.
Conclusions:
We herein conclude that serum KD-specific molecules were mostly derived from biofilms and possessed molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus. Discovery of these KD-specific molecules might offer novel insight into the diagnosis and management of KD as well as its pathogenesis.
Insights
Researchers identified specific microbe-associated molecular patterns (MAMPs) in Kawasaki disease (KD) patient sera, primarily derived from bacterial biofilms. These MAMPs may play a key role in KD pathogenesis and offer potential diagnostic insights.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Kawasaki disease (KD) is a critical pediatric vasculitis with an unknown cause, involving the innate immune system during its acute phase.
- A novel murine model for KD coronary arteritis was developed using oral administration of synthetic microbe-associated molecular patterns (MAMPs).
- This study hypothesized the existence of specific MAMPs in KD sera to identify disease-specific molecules and elucidate pathogenesis.
Purpose of the Study:
- To identify specific MAMPs in Kawasaki disease (KD) patient sera.
- To investigate the origin and molecular characteristics of KD-specific molecules.
- To assess the potential role of these molecules in KD pathogenesis.
Main Methods:
- Liquid chromatography-mass spectrometry (LC-MS) was used to analyze serum samples from KD patients and controls.
- Biofilm samples were evaluated using microbiological and LC-MS techniques.
- Human coronary artery endothelial cells (HCAECs) were used to assess cytokine responses.
Main Results:
- KD serum samples revealed specific molecules in lipophilic fractions with distinct mass spectrometry patterns, correlating with MAMPs from various bacterial biofilms.
- These identified MAMPs, derived from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis, and Staphylococcus aureus, induced proinflammatory cytokine release in HCAECs.
- Some KD-specific serum molecules demonstrated binding to IgG, suggesting an immune interaction.
Conclusions:
- Serum KD-specific molecules are largely derived from bacterial biofilms and share structural similarities with MAMPs from common bacteria.
- The identified MAMPs may be crucial in the pathogenesis of Kawasaki disease.
- These findings offer potential for novel diagnostic and therapeutic strategies for KD.
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