Frontiers in immunology · 2026
Association of elevated serum active IL-18 levels with cytokine profiles and clinical features in adult-onset still's disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Yoshida Shuhei, Matsumoto Haruki, Fujita Yuya, Sumichika Yuya, Saito Kenji, Asano Tomoyuki, Sato Shuzo, Mizokami Masashi, Sugiyama Masaya, Shimojima Yasuhiro, Kawakami Atsushi, Migita Kiyoshi
Аннотация
INTRODUCTION: Inflammasome-mediated activation of interleukin (IL)-1β and IL-18 plays a key role in the pathogenesis of adult-onset Still's disease (AOSD), a systemic autoinflammatory disorder. The cleaved free active form of IL-18 may more accurately reflect inflammasome activity than total IL-18, which includes pro-IL-18, free active IL-18, and IL-18 bound to IL-18-binding protein. This study aimed to measure serum active IL-18 levels in patients with AOSD and evaluate their clinical and diagnostic significance.
METHODS: Serum samples were obtained from 47 untreated patients with AOSD, 42 patients with rheumatoid arthritis (RA), 9 patients with familial Mediterranean fever (FMF), and 26 healthy controls (HCs). Active IL-18 was quantified using a specific ELISA detecting cleaved, biologically active IL-18, and 69 cytokines were analyzed in patients with AOSD using a multiplex suspension array. Correlations between active IL-18 and other cytokines, clinical parameters, and the reactive hemophagocytic syndrome diagnostic score (HScore) were evaluated, and discriminative performance was assessed using receiver operating characteristic analysis.
RESULTS: Serum levels of active IL-18 were significantly higher in patients with AOSD than in those with RA, FMF, and HCs (all p < 0.001). Active IL-18 levels positively correlated with the Pouchot score (p < 0.001), serum ferritin level (p = 0.004), and C-reactive protein level (p = 0.004) and decreased significantly after immunosuppressive therapy (p = 0.003). Active IL-18 significantly and positively correlated with total IL-18, macrophage colony-stimulating factor, basic fibroblast growth factor, leukemia inhibitory factor, chemokine (C-X-C motif) ligand 9, and IL-12 (p40), all of which were significantly correlated with the HScore. Elevated active IL-18 levels were associated with rashes and splenomegaly. Among the evaluated biomarkers, active IL-18 showed the highest diagnostic accuracy for AOSD (cutoff > 4,231.1 pg/mL; sensitivity, 89.4%; specificity, 92.9%; area under the curve 0.963).
CONCLUSIONS: Serum active IL-18 levels were significantly higher in patients with AOSD than in HCs and in patients with FMF or RA. Active IL-18 levels were associated with clinical features such as rash and splenomegaly and correlated with specific cytokines. Serum active IL-18 levels may serve as a biomarker of inflammasome activation and disease activity in patients with AOSD.
METHODS: Serum samples were obtained from 47 untreated patients with AOSD, 42 patients with rheumatoid arthritis (RA), 9 patients with familial Mediterranean fever (FMF), and 26 healthy controls (HCs). Active IL-18 was quantified using a specific ELISA detecting cleaved, biologically active IL-18, and 69 cytokines were analyzed in patients with AOSD using a multiplex suspension array. Correlations between active IL-18 and other cytokines, clinical parameters, and the reactive hemophagocytic syndrome diagnostic score (HScore) were evaluated, and discriminative performance was assessed using receiver operating characteristic analysis.
RESULTS: Serum levels of active IL-18 were significantly higher in patients with AOSD than in those with RA, FMF, and HCs (all p < 0.001). Active IL-18 levels positively correlated with the Pouchot score (p < 0.001), serum ferritin level (p = 0.004), and C-reactive protein level (p = 0.004) and decreased significantly after immunosuppressive therapy (p = 0.003). Active IL-18 significantly and positively correlated with total IL-18, macrophage colony-stimulating factor, basic fibroblast growth factor, leukemia inhibitory factor, chemokine (C-X-C motif) ligand 9, and IL-12 (p40), all of which were significantly correlated with the HScore. Elevated active IL-18 levels were associated with rashes and splenomegaly. Among the evaluated biomarkers, active IL-18 showed the highest diagnostic accuracy for AOSD (cutoff > 4,231.1 pg/mL; sensitivity, 89.4%; specificity, 92.9%; area under the curve 0.963).
CONCLUSIONS: Serum active IL-18 levels were significantly higher in patients with AOSD than in HCs and in patients with FMF or RA. Active IL-18 levels were associated with clinical features such as rash and splenomegaly and correlated with specific cytokines. Serum active IL-18 levels may serve as a biomarker of inflammasome activation and disease activity in patients with AOSD.