Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome

Kaneko, S; Hatano, M; Shimbo, A; Miyaoka, F; Irabu, H; Akutsu, Y; Hayashi, Y; Mizuta, M; Nakagishi, Y; Akamine, K; Iwata, N; Furuno, K; Tanaka, T; Ueno, K; Fujita, S; Yokoyama, K; Minato, T; Izawa, K; Yasumi, T; Matsubayashi, T; Hosoya, T; Nishikawa, H; Fujimura, J; Asano, R; Sugita, Y; Watanabe, K; Kobayashi, A; Endo, T; Eguchi, K; Nishikomori, R; Yasuoka, R; Asano, T; Kanno, M; Hamada, K; Fujita, Y; Hayashi, D; Watanabe, S; Shiba, T; Yasuda, S; Mori, M; Kanegane, H; Takagi, M; Shimizu, M

doi:10.1002/art.43349

Pediatric rheumatology

Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome

Arthritis RheumatolPublished 30 Nov 2025Cross-sectional study

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Authors' conclusion

Serum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.

Study context

Population: Adult and pediatric patients with cytokine storm syndrome (CSS) (primary and secondary hemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD)-like hyperinflammatory syndromes) and healthy controls143 CSS, 22 healthy controls
Participants: 165 participants

Exposure: Serum cytokine profiles across underlying diseases of CSS and healthy controls
Outcome: Serum cytokine profiles (IFN-α, IL-18, IL-6, CXCL9, sTNF-RII) distinguishing underlying diseases of CSS

Methodological detailsbead-based multiplex immunoassay (Luminex), enzyme-linked immunosorbent assay (ELISA)

Bead-based multiplex immunoassay (Luminex)
ELISA

Main finding

As reported in the abstract

Serum cytokine patterns by underlying disease

Luminex assay (48 cytokines, 97 patients) categorized CSS patients into five clusters: 5

Observational data: associations, not effects.

Reference

Authors: Kaneko S, Hatano M, Shimbo A, Miyaoka F, Irabu H, Akutsu Y, et al.
All 43 authors
Kaneko S, Hatano M, Shimbo A, Miyaoka F, Irabu H, Akutsu Y, Hayashi Y, Mizuta M, Nakagishi Y, Akamine K, Iwata N, Furuno K, Tanaka T, Ueno K, Fujita S, Yokoyama K, Minato T, Izawa K, Yasumi T, Matsubayashi T, Hosoya T, Nishikawa H, Fujimura J, Asano R, Sugita Y, Watanabe K, Kobayashi A, Endo T, Eguchi K, Nishikomori R, Yasuoka R, Asano T, Kanno M, Hamada K, Fujita Y, Hayashi D, Watanabe S, Shiba T, Yasuda S, Mori M, Kanegane H, Takagi M, Shimizu M
Journal: Arthritis & Rheumatology
Published: 30 Nov 2025
DOI: 10.1002/art.43349
PubMed: 40776831

Topic: Pediatric rheumatology

Key notes

Elevated IFN-α in histiocytic necrotizing lymphadenitis-associated HLH and SLE-associated macrophage activation syndrome (MAS)
Higher IL-18 in sJIA- and AOSD-associated MAS, XIAP deficiency with HLH and NLRC4-associated autoinflammatory disorder

More notes

Higher IL-6 in KD shock syndrome than the other groups
CXCL9 significantly elevated in virus-associated HLH, familial HLH, malignant lymphoma-associated HLH and KD-MAS
Moderate elevations of CXCL9 and IL-6 in multisystem inflammatory syndrome in children and toxic shock syndrome

Original publication

Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome. Arthritis Rheumatol. Published 30 November 2025. doi:10.1002/art.43349

Read the original article ↗

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