{"id":62221,"date":"2026-04-20T12:00:00","date_gmt":"2026-04-20T10:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/04\/20\/trem-1-associated-neutrophil-extracellular-trap-formation-is-linked-to-ivig-resistance-in-kawasaki-disease-a-convergent-transcriptomic-and-prospective-validation-study\/"},"modified":"2026-04-20T12:00:00","modified_gmt":"2026-04-20T10:00:00","slug":"trem-1-associated-neutrophil-extracellular-trap-formation-is-linked-to-ivig-resistance-in-kawasaki-disease-a-convergent-transcriptomic-and-prospective-validation-study","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/04\/20\/trem-1-associated-neutrophil-extracellular-trap-formation-is-linked-to-ivig-resistance-in-kawasaki-disease-a-convergent-transcriptomic-and-prospective-validation-study\/","title":{"rendered":"TREM-1-Associated Neutrophil Extracellular Trap Formation is Linked to IVIG Resistance in Kawasaki Disease: A Convergent Transcriptomic and Prospective Validation Study"},"content":{"rendered":"
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J Clin Immunol<\/b>. 2026 Apr 21. doi: 10.1007\/s10875-026-02025-x. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

Kawasaki disease (KD) remains the leading cause of acquired heart disease in children. While intravenous immunoglobulin (IVIG) represents standard therapy, approximately 10-20% of patients exhibit treatment refractoriness associated with significantly elevated coronary artery lesion risk. Current risk stratification relies on clinical parameters-fever duration or nonspecific inflammatory markers-which fail to capture distinct immunopathological features associated with treatment failure. To bridge this gap, we employed a convergent strategy integrating transcriptomic discovery from two independent cohorts with prospective protein-level and cellular validation in a clinical cohort. Three machine learning models-LASSO regression, Random Forest, and XGBoost-independently identified TREM1 (Triggering Receptor Expressed on Myeloid cells-1) as a core resistance predictor. Prospective validation in 117 KD patients demonstrated that plasma soluble TREM-1 (sTREM-1) was markedly elevated in IVIG-resistant cases (median 1247 vs. 856 pg\/mL, P < 0.001) and effectively differentiated KD from other febrile illnesses. Mechanistically, sTREM-1 elevation showed a moderate positive correlation with myeloperoxidase-DNA complexes (\u03c1 = 0.612, P < 0.001), indicating that TREM-1-associated neutrophil hyperactivation is associated with excessive neutrophil extracellular trap (NET) formation and vascular injury. External validation (GSE63881) confirmed TREM1 upregulation (2.1-fold) in resistant patients. Incorporating sTREM-1 into a multivariable prediction model achieved area under curve 0.884 using Firth’s penalized logistic regression (optimism-corrected AUC 0.871) in this derivation cohort, significantly outperforming traditional clinical scores. These findings suggest TREM-1-associated NETosis as a potential contributor to the pathobiology of IVIG resistance. As a TRIPOD Type 1b derivation study, external clinical validation in independent multi-center cohorts is required prior to clinical implementation.<\/p>\n

PMID:42010185<\/a> | DOI:10.1007\/s10875-026-02025-x<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Clin Immunol. 2026 Apr 21. doi: 10.1007\/s10875-026-02025-x. Online ahead of print. ABSTRACT Kawasaki disease (KD) remains the leading cause of acquired heart disease in children. While intravenous immunoglobulin (IVIG) represents standard therapy, approximately 10-20% of patients exhibit treatment refractoriness associated with significantly elevated coronary artery lesion risk. Current risk stratification relies on clinical parameters-fever … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-62221","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/62221","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=62221"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/62221\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=62221"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=62221"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=62221"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}