{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:06:01Z","timestamp":1790867161087,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370511"],"award-info":[{"award-number":["82370511"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intravenous immunoglobulin (IVIG) has been established as the first-line treatment for Kawasaki disease (KD). However, 10%\u201320% of patients are unresponsive, increasing their risk of coronary artery complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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, the expression of key cytokines was validated using public bulk RNA-seq data and enzyme-linked immunosorbent assay (ELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Non-responders exhibited elevated inflammatory cells, lymphocyte dysfunction, and a stronger inflammatory cytokine response driven by the S100A12\u2013TLR4\u2013MYD88 axis, initiated by Mono_CD14_CD16 cells, which was closely associated with interferon activation. Despite T\/NK-cell exhaustion, cytotoxic activity was preserved. All processes appeared to be closely associated with interferon activation. Disrupted Tfh\u2013B-cell coordination was observed alongside plasmablast enrichment. Furthermore, monocytic myeloid-derived suppressor cells (MDSCs) suppressed T-cell function and promoted inflammation. The expression levels of S100A8\/A9, S100A12, TNF, TNFSF8\/10, and interferon-\u03b1 were consistent with the transcriptomic data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal the immune landscape in IVIG non-responsive KD and suggest potential targets for alternative therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1702290","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:29:47Z","timestamp":1764224987000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Single-cell transcriptomic analysis reveals a systemic immune dysregulation in intravenous immunoglobulin non-responsive Kawasaki 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