ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Single-cell transcriptomic analysis reveals a systemic immune dysregulation in intravenous immunoglobulin non-responsive Kawasaki disease
Provisionally accepted
- 1Peking University, Beijing, China
- 2Department of Cardiovascular Medicine, Capital Center for Children’s Health, Capital Medical University, Beijing, China
- 3Department of Cardiology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing, China
- 4Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College., Beijing, China
- 5Department of pediatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine,Tsinghua University., Beijing, China
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Background:Intravenous immunoglobulin (IVIG) has been established as the first-line treatment for Kawasaki disease (KD). However, 10–20% of patients are unresponsive, increasing their risk of coronary artery complications. Methods: To elucidate the pathogenesis of IVIG non-responsiveness, we performed single-cell transcriptomic profiling on 24 peripheral blood mononuclear cell (PBMC) samples from responsive and non-responsive KD patients before and after IVIG treatment. Finally, public bulk RNA-seq data and enzyme-linked immunosorbent assay (ELISA) were conducted to validate the expression of key cytokines. Results: Non-responders exhibited elevated inflammatory cells, lymphocyte dysfunction, and a stronger inflammatory cytokine response driven by the S100A12–TLR4–MYD88 axis, initiated by Mono_CD14_CD16 cells, which was closely associated with interferon activation. Despite T/NK cell exhaustion, cytotoxic activity was preserved. All process appeared to be closely associated with interferon activation. Disrupted Tfh–B cell coordination was observed alongside plasmablast enrichment. Besides, monocytic myeloid-derived suppressor cells (MDSCs) suppressed T cells function and promoted inflammation. Expression levels of S100A8/A9, S100A12, TNF, TNFSF8/10, and interferon-α were consistent with the transcriptomic data. Conclusions:Our findings reveal the immune landscape in IVIG non-responsive KD and suggest potential targets for alternative therapies.
Keywords: kawasaki disease, Single-cell transcriptomic analysis, IVIG non-responsive, Inflammatory cytokine response, T/NK cell exhaustion, interferon
Received: 09 Sep 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Feng, Qirui, Yang, Chen, Zhang, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaohui Li, lxhmaggie@pumc.edu.cn
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