{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:59:53Z","timestamp":1792652393758,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Objective<\/jats:title>\n Cytokine storm syndrome (CSS), commonly associated with hemophagocytic lymphohistiocytosis (HLH), is a fatal hyperinflammatory syndrome. Differentiating the underlying diseases responsible for CSS is essential for timely therapeutic decisions. This study explored the clinical usefulness of serum cytokine profiling in distinguishing underlying diseases in patients with CSS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Serum samples were collected from 143 adult and pediatric patients with CSS and 22 healthy controls. The cohort included patients with various diagnoses of primary and secondary HLH and Kawasaki disease (KD)\u2010like hyperinflammatory syndromes. Serum levels of 48 cytokines were analyzed in 97 patients using a bead\u2010based multiplex immunoassay (Luminex assay). Serum levels of interferon alpha (IFN\u2010\u03b1), interleukin\u201018 (IL\u201018), IL\u20106, CXCL9, and soluble tumor necrosis factor receptor II (sTNF\u2010RII) were measured in 165 participants using enzyme\u2010linked immunosorbent assay (ELISA).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Luminex assay categorized patients with CSS into five clusters based on serum cytokine patterns. ELISA revealed distinct cytokine patterns, wherein patients with histiocytic necrotizing lymphadenitis\u2010associated HLH and systemic lupus erythematosus\u2010associated macrophage activation syndrome (MAS) showed elevated IFN\u2010\u03b1; systemic juvenile idiopathic arthritis\u2013associated and adult\u2010onset Still's disease\u2013associated MAS, X\u2010linked inhibitor of apoptosis protein deficiency with HLH, and NLRC4\u2010associated autoinflammatory disorder exhibited higher IL\u201018 levels. Additionally, KD shock syndrome had higher IL\u20106 levels than the other groups. CXCL9 was significantly elevated in patients with virus\u2010associated HLH, familial HLH, malignant lymphoma\u2010associated HLH, and KD\u2010MAS. Multisystem inflammatory syndrome in children and toxic shock syndrome also showed moderate elevations of CXCL9 and IL\u20106 levels.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Serum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.43349","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T08:40:33Z","timestamp":1754642433000},"page":"463-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8840-5373","authenticated-orcid":false,"given":"Shuya","family":"Kaneko","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Developmental Biology Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Developmental Biology Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asami","family":"Shimbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Developmental Biology Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Tokyo 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