{"title":"Serum cytokine profiling differentiates underlying diseases in cytokine storm syndrome.","authors":"Shuya Kaneko,Maho Hatano,Asami Shimbo,Futaba Miyaoka,Hitoshi Irabu,Yuko Akutsu,Yuko Hayashi,Mao Mizuta,Yasuo Nakagishi,Keiji Akamine,Naomi Iwata,Kenji Furuno,Takayuki Tanaka,Kazuyuki Ueno,Shuhei Fujita,Koji Yokoyama,Toshinori Minato,Kazushi Izawa,Takahiro Yasumi,Tadashi Matsubayashi,Tadashi Hosoya,Hiroki Nishikawa,Junya Fujimura,Ryoko Asano,Yuko Sugita,Kenichi Watanabe,Anna Kobayashi,Takuya Endo,Katsuhide Eguchi,Ryuta Nishikomori,Ryuhei Yasuoka,Takaki Asano,Miyako Kanno,Kazuya Hamada,Yuji Fujita,Daisuke Hayashi,Shojiro Watanabe,Takeshi Shiba,Shinsuke Yasuda,Masaaki Mori,Hirokazu Kanegane,Masatoshi Takagi,Masaki Shimizu","doi":"10.1002/art.43349","DOIUrl":null,"url":null,"abstract":"OBJECTIVE\r\nCytokine 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.\r\n\r\nMETHODS\r\nSerum 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 IFN-α, IL-18, IL-6, CXCL9, and sTNF-RII were measured in 165 participants using enzyme-linked immunosorbent assay (ELISA).\r\n\r\nRESULTS\r\nLuminex 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-MAS showed elevated IFN-α; systemic juvenile idiopathic arthritis- and adult-onset Still's disease-associated MAS, XIAP 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.\r\n\r\nCONCLUSION\r\nSerum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"156 1","pages":""},"PeriodicalIF":10.9000,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthritis & Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/art.43349","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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 IFN-α, IL-18, IL-6, CXCL9, and 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-MAS showed elevated IFN-α; systemic juvenile idiopathic arthritis- and adult-onset Still's disease-associated MAS, XIAP 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.
期刊介绍:
Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.