Background <p>Kawasaki disease (KD) is a systemic vasculitis that causes coronary artery lesions (CAL). Its clinical overlap with multisystem inflammatory syndrome in children (MIS-C) complicates differential diagnosis. The distinct immunopathologies and specific drivers of CAL, are not fully understood. This study aimed to clarify inflammatory cytokine differences between KD and MIS-C, and to identify molecules involved in CAL.</p> Methods <p>We measured 48 serum cytokines in 20 patients with KD (6 with CAL), 22 patients with MIS-C, and 9 healthy controls using a Luminex assay. The effects of cytokines on human coronary artery endothelial cells (HCAECs) were evaluated in vitro, assessing expression of angiogenic and adhesion molecules by RT-qPCR.</p> Results <p>Fifteen cytokines differed significantly between KD and MIS-C. GRO-1α was the most effective biomarker for differentiation between KD and MIS-C. In KD, eight cytokines (including G-CSF, IL-6, and IL-17A) were elevated in cases with CAL. In vitro, IL-17A induced <i>VEGF</i> expression, IL-6 altered <i>ANGPT1/2</i> balance, and G-CSF upregulated <i>ICAM1</i> in HCAECs, suggesting distinct contributions to CAL development.</p> Conclusion <p>GRO-1α is a robust biomarker for distinguishing KD from MIS-C. IL-17A, IL-6, and G-CSF are key cytokines in CAL development. These findings advance KD pathogenesis understanding and may improve diagnosis and targeted therapies.</p> Impact Statement <p><UnorderedList Mark="Bullet"> <ItemContent> <p>GRO-1α (CXCL1) is identified as a novel biomarker that distinguishes Kawasaki disease (KD) from MIS-C.</p> </ItemContent> <ItemContent> <p>In patients with KD, elevated GRO-1α levels correlate with coronary artery lesion (CAL) development. In vitro, IL-6, IL-17A, and G-CSF induce pro-inflammatory responses in human coronary artery endothelial cells (HCAECs), linking these cytokines to vascular injury.</p> </ItemContent> <ItemContent> <p>GRO-1α and these cytokine pathways could serve as new biomarkers or therapeutic targets to increase diagnostic accuracy and prevent CAL. Targeting IL-6, IL-17A or G-CSF signaling may mitigate KD-associated vascular inflammation, suggesting new therapeutic strategies to reduce coronary damage.</p> </ItemContent> </UnorderedList></p>

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Serum cytokine profiling reveals distinct inflammatory signatures in Kawasaki disease and MIS-C and suggests associations with coronary artery lesions

  • Shuya Kaneko,
  • Maho Hatano,
  • Asami Shimbo,
  • Koji Yokoyama,
  • Kenji Furuno,
  • Takayuki Tanaka,
  • Shuhei Fujita,
  • Naomi Iwata,
  • Junya Fujimura,
  • Keiji Akamine,
  • Mao Mizuta,
  • Yasuo Nakagishi,
  • Toshinori Minato,
  • Satoshi Okada,
  • Masaaki Mori,
  • Masaki Shimizu

摘要

Background

Kawasaki disease (KD) is a systemic vasculitis that causes coronary artery lesions (CAL). Its clinical overlap with multisystem inflammatory syndrome in children (MIS-C) complicates differential diagnosis. The distinct immunopathologies and specific drivers of CAL, are not fully understood. This study aimed to clarify inflammatory cytokine differences between KD and MIS-C, and to identify molecules involved in CAL.

Methods

We measured 48 serum cytokines in 20 patients with KD (6 with CAL), 22 patients with MIS-C, and 9 healthy controls using a Luminex assay. The effects of cytokines on human coronary artery endothelial cells (HCAECs) were evaluated in vitro, assessing expression of angiogenic and adhesion molecules by RT-qPCR.

Results

Fifteen cytokines differed significantly between KD and MIS-C. GRO-1α was the most effective biomarker for differentiation between KD and MIS-C. In KD, eight cytokines (including G-CSF, IL-6, and IL-17A) were elevated in cases with CAL. In vitro, IL-17A induced VEGF expression, IL-6 altered ANGPT1/2 balance, and G-CSF upregulated ICAM1 in HCAECs, suggesting distinct contributions to CAL development.

Conclusion

GRO-1α is a robust biomarker for distinguishing KD from MIS-C. IL-17A, IL-6, and G-CSF are key cytokines in CAL development. These findings advance KD pathogenesis understanding and may improve diagnosis and targeted therapies.

Impact Statement

GRO-1α (CXCL1) is identified as a novel biomarker that distinguishes Kawasaki disease (KD) from MIS-C.

In patients with KD, elevated GRO-1α levels correlate with coronary artery lesion (CAL) development. In vitro, IL-6, IL-17A, and G-CSF induce pro-inflammatory responses in human coronary artery endothelial cells (HCAECs), linking these cytokines to vascular injury.

GRO-1α and these cytokine pathways could serve as new biomarkers or therapeutic targets to increase diagnostic accuracy and prevent CAL. Targeting IL-6, IL-17A or G-CSF signaling may mitigate KD-associated vascular inflammation, suggesting new therapeutic strategies to reduce coronary damage.