Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.

Objective: 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 o...

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Published in:Arthritis & Rheumatology Vol. 78; no. 2; pp. 463 - 475
Main Authors: Kaneko, Shuya, Hatano, Maho, Shimbo, Asami, Miyaoka, Futaba, Irabu, Hitoshi, Akutsu, Yuko, Hayashi, Yuko, Mizuta, Mao, Nakagishi, Yasuo, Akamine, Keiji, Iwata, Naomi, Furuno, Kenji, Tanaka, Takayuki, Ueno, Kazuyuki, Fujita, Shuhei, Yokoyama, Koji, Minato, Toshinori, Izawa, Kazushi, Yasumi, Takahiro, Matsubayashi, Tadashi
Format: research tables/charts Journal Article
Published: Wiley-Blackwell Feb2026
Online Access:View this record in EBSCOhost
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      dt: Feb2026
      vid: 78
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1002/art.43349
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        atl: Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.
      aug:
        au:
          Kaneko, Shuya
          Hatano, Maho
          Shimbo, Asami
          Miyaoka, Futaba
          Irabu, Hitoshi
          Akutsu, Yuko
          Hayashi, Yuko
          Mizuta, Mao
          Nakagishi, Yasuo
          Akamine, Keiji
          Iwata, Naomi
          Furuno, Kenji
          Tanaka, Takayuki
          Ueno, Kazuyuki
          Fujita, Shuhei
          Yokoyama, Koji
          Minato, Toshinori
          Izawa, Kazushi
          Yasumi, Takahiro
          Matsubayashi, Tadashi
        affil: Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
      sug:
        subj:
          Cytokine Release Syndrome Etiology
          Cytokine Release Syndrome Diagnosis
          Cytokines Blood
          Classification Algorithms
          Macrophage Activation Syndrome
          Hemophagocytic Lymphohistiocytosis
          Diagnosis, Differential
          Human
          Male
          Female
          Infant, Newborn
          Infant
          Child, Preschool
          Child
          Adolescence
          Adult
          Middle Age
          Aged
          Aged, 80 and Over
          Japan
          Multicenter Studies
          Nonexperimental Studies
          Enzyme-Linked Immunosorbent Assay
          Immunoassay
          Retrospective Design
          Record Review
          Medical Records
          Tumor Necrosis Factor
          Interleukins
          Intracellular Signaling Peptides and Proteins
          ROC Curve
          Sensitivity and Specificity
          Predictive Value of Tests
          Kruskal-Wallis Test
          Mann-Whitney U Test
          Paired T-Tests
          Pearson's Correlation Coefficient
          Descriptive Statistics
          Data Analysis Software
          Cytokine Release Syndrome Classification
          Cytokine Release Syndrome Therapy
          Immune System
          Infant, Newborn: birth-1 month
          Infant: 1-23 months
          Child, Preschool: 2-5 years
          Child: 6-12 years
          Adolescent: 13-18 years
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Aged, 80 & over
          Male
          Female
      ab: Objective: 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. Methods: 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)‐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). Results: 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‐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. Conclusion: Serum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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