ArticleArthritis & rheumatology (Hoboken, N.J.)2026
Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Hemophagocytic lymphohistiocytosis in critically ill patients: A guide for clinicians.World journal of critical care medicine · 2026Review
- The value of C-X-C motif chemokine ligand 9 (CXCL9) in the differential diagnosis and management of haemophagocytic lymphohistiocytosis.British journal of haematology · 2026Article
- Macrophage activation syndrome in systemic lupus erythematous and Still's disease: distinct phenotypes shaped by the underlying diseases.Rheumatology (Oxford, England) · 2026Article
- Beyond the Storm: CXCL9 and the New Era of Precision Hemophagocytic Lymphohistiocytosis Diagnostics.Diagnostics (Basel, Switzerland) · 2026Review
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Elevated nil values in TB-IGRA: a potential diagnostic clue for pediatric histiocytic necrotizing lymphadenitis.Pediatric rheumatology online journal · 2026Article
- The Co-Evolutionary Arms Race BetweenMicroorganisms · 2026Review
- Childhood-Onset Systemic Lupus Erythematosus Research over the Past Decade in Japan.Children (Basel, Switzerland) · 2026Review
- The many faces of cytokine storm syndrome: immunopathogenic mechanisms and clinical implications for a better patient management.Clinical and experimental immunology · 2026Review
Corrections and comments
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Authors and funding
43 authors.
Funding
Abstract
objectiveCytokine 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.
methodsSerum 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)-like hyperinflammatory syndromes. Serum levels of 48 cytokines were analyzed in 97 patients using a bead-based multiplex immunoassay (Luminex assay). Serum levels of interferon alpha (IFN-α), interleukin-18 (IL-18), IL-6, CXCL9, and soluble tumor necrosis factor receptor II (sTNF-RII) were measured in 165 participants using enzyme-linked immunosorbent assay (ELISA).
resultsLuminex assay categorized patients with CSS into five clusters based on serum cytokine patterns. ELISA revealed distinct cytokine patterns, wherein patients with histiocytic necrotizing lymphadenitis-associated HLH and systemic lupus erythematosus-associated macrophage activation syndrome (MAS) showed elevated IFN-α; systemic juvenile idiopathic arthritis-associated and adult-onset Still's disease-associated MAS, X-linked inhibitor of apoptosis protein deficiency with HLH, and NLRC4-associated autoinflammatory disorder exhibited higher IL-18 levels. Additionally, KD shock syndrome had higher IL-6 levels than the other groups. CXCL9 was significantly elevated in patients with virus-associated HLH, familial HLH, malignant lymphoma-associated HLH, and KD-MAS. Multisystem inflammatory syndrome in children and toxic shock syndrome also showed moderate elevations of CXCL9 and IL-6 levels.
conclusionSerum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.
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Registered trials
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