Kawasaki disease-specific molecules in the sera are linked to microbe-associated molecular patterns in the biofilms

Takeshi Kusuda, Yasutaka Nakashima, Kenji Murata, Shunsuke Kanno, Hisanori Nishio, Mitsumasa Saito, Tamami Tanaka, Kenichiro Yamamura, Yasunari Sakai, Hidetoshi Takada, Tomofumi Miyamoto, Yumi Mizuno, Kazunobu Ouchi, Kenji Waki, Toshiro Hara

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number0113054
JournalPloS one
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 20 2014

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Mucocutaneous Lymph Node Syndrome
Yersinia pseudotuberculosis
Biofilms
Bacillus cereus
biofilm
Staphylococcus aureus
microorganisms
Molecules
Bacillus subtilis
liquid chromatography
Serum
coronary vessels
mass spectrometry
endothelial cells
cytokines
pathogenesis
arteritis
sampling
Liquid chromatography
vasculitis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kawasaki disease-specific molecules in the sera are linked to microbe-associated molecular patterns in the biofilms. / Kusuda, Takeshi; Nakashima, Yasutaka; Murata, Kenji; Kanno, Shunsuke; Nishio, Hisanori; Saito, Mitsumasa; Tanaka, Tamami; Yamamura, Kenichiro; Sakai, Yasunari; Takada, Hidetoshi; Miyamoto, Tomofumi; Mizuno, Yumi; Ouchi, Kazunobu; Waki, Kenji; Hara, Toshiro.

In: PloS one, Vol. 9, No. 11, 0113054, 20.11.2014.

Research output: Contribution to journalArticle

Kusuda, T, Nakashima, Y, Murata, K, Kanno, S, Nishio, H, Saito, M, Tanaka, T, Yamamura, K, Sakai, Y, Takada, H, Miyamoto, T, Mizuno, Y, Ouchi, K, Waki, K & Hara, T 2014, 'Kawasaki disease-specific molecules in the sera are linked to microbe-associated molecular patterns in the biofilms', PloS one, vol. 9, no. 11, 0113054. https://doi.org/10.1371/journal.pone.0113054
Kusuda, Takeshi ; Nakashima, Yasutaka ; Murata, Kenji ; Kanno, Shunsuke ; Nishio, Hisanori ; Saito, Mitsumasa ; Tanaka, Tamami ; Yamamura, Kenichiro ; Sakai, Yasunari ; Takada, Hidetoshi ; Miyamoto, Tomofumi ; Mizuno, Yumi ; Ouchi, Kazunobu ; Waki, Kenji ; Hara, Toshiro. / Kawasaki disease-specific molecules in the sera are linked to microbe-associated molecular patterns in the biofilms. In: PloS one. 2014 ; Vol. 9, No. 11.
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AU - Kusuda, Takeshi

AU - Nakashima, Yasutaka

AU - Murata, Kenji

AU - Kanno, Shunsuke

AU - Nishio, Hisanori

AU - Saito, Mitsumasa

AU - Tanaka, Tamami

AU - Yamamura, Kenichiro

AU - Sakai, Yasunari

AU - Takada, Hidetoshi

AU - Miyamoto, Tomofumi

AU - Mizuno, Yumi

AU - Ouchi, Kazunobu

AU - Waki, Kenji

AU - Hara, Toshiro

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N2 - 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.

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