Related Experiment Video
Updated: Sep 12, 2025
Author Spotlight: Unveiling the Polyfunctionality and Heterogeneity in Immune Responses
Published on: March 8, 2024
Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome
Shuya Kaneko1, Maho Hatano1, Asami Shimbo1
1Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Insights
Serum cytokine profiling helps distinguish subtypes of cytokine storm syndrome (CSS), a severe hyperinflammatory condition. This aids in diagnosing underlying diseases like hemophagocytic lymphohistiocytosis (HLH) for tailored treatments.
Area of Science:
- Immunology
- Clinical Medicine
- Biochemistry
Background:
- Cytokine storm syndrome (CSS) is a life-threatening hyperinflammatory state, often linked to hemophagocytic lymphohistiocytosis (HLH).
- Accurate differentiation of underlying causes of CSS is crucial for initiating prompt and effective therapeutic interventions.
- Identifying specific etiological drivers of CSS is a significant clinical challenge.
Purpose of the Study:
- To evaluate the clinical utility of serum cytokine profiling in differentiating various underlying diseases causing CSS.
- To explore distinct cytokine signatures associated with different CSS subtypes.
Main Methods:
- Serum samples were collected from 143 patients with CSS and 22 healthy controls.
- Cytokine levels (48 analytes) were measured using Luminex assay in 97 patients.
- Specific cytokines (IFN-α, IL-18, IL-6, CXCL9, sTNF-RII) were quantified via ELISA in 165 participants.
Main Results:
- Serum cytokine patterns, analyzed by Luminex, revealed five distinct patient clusters.
- ELISA identified specific cytokine elevations: IFN-α in HLH-associated with histiocytic necrotizing lymphadenitis and SLE-MAS; IL-18 in sJIA/ASD-MAS, XIAP deficiency-HLH, and NLRC4-autoinflammatory disorder.
- Elevated IL-6 was observed in KD shock syndrome, while CXCL9 was significantly increased in virus-associated HLH, familial HLH, lymphoma-associated HLH, and KD-MAS.
Conclusions:
- Serum cytokine profiling serves as an effective tool for differentiating CSS subtypes.
- This approach can guide more precise diagnoses and inform personalized treatment strategies for CSS patients.
- Understanding specific cytokine signatures aids in tailoring therapies based on the underlying disease etiology.
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.
More Related Videos
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
01:20The JAK-STAT Signaling Pathway