Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
PLoS One. 2024 Jul 29;19(7):e0307908. doi: 10.1371/journal.pone.0307908. eCollection 2024.
Caspase-1 is a crucial component in the inflammasome activation cascade. This study evaluated the potential of serum caspase-1 level as an inflammatory biomarker in patients with adult-onset Still's disease (AOSD).
The study included 51 consecutive patients diagnosed with AOSD based on the Yamaguchi criteria, 66 patients with rheumatoid arthritis (RA) as disease control, and 36 healthy controls (HCs). Serum caspase-1 concentrations were measured using enzyme-linked immunosorbent assay. The serum 69 cytokine levels were analyzed using a multisuspension cytokine array in patients with AOSD, and a cluster analysis of each cytokine was performed to determine specific molecular networks.
Patients with AOSD had significantly increased serum caspase-1 levels versus patients with RA (p < 0.001) and HCs (p < 0.001). Additionally, serum caspase-1 demonstrated significant positive correlations with AOSD disease activity score (Pouchot score, r = 0.59, p < 0.001) and serum ferritin (r = 0.54, p < 0.001). Furthermore, among patients with AOSD, significant correlations existed between serum caspase-1 and inflammatory cytokines, including interleukin-18. Immunoblot analysis detected the cleaved form of caspase-1 (p20) in the serum of untreated patients with AOSD, not in those from patients with inactive AOSD receiving immunosuppressive treatments.
Caspase-1 is a useful biomarker for AOSD diagnosis and monitoring. Caspase-1 activation could be correlated with the inflammatory component of AOSD, specifically through proinflammatory cytokine induction via inflammasome activation cascades.
Caspase-1 是炎症小体激活级联反应中的关键组成部分。本研究评估了血清 Caspase-1 水平作为成人Still 病（AOSD）患者炎症生物标志物的潜力。
该研究纳入了 51 例根据 Yamaguchi 标准诊断为 AOSD 的连续患者、66 例类风湿关节炎（RA）患者作为疾病对照和 36 例健康对照。采用酶联免疫吸附试验检测血清 Caspase-1 浓度。采用多悬浮细胞因子阵列分析 AOSD 患者的血清 69 种细胞因子水平，并对每种细胞因子进行聚类分析，以确定特定的分子网络。
与 RA 患者（p<0.001）和 HC 相比，AOSD 患者的血清 Caspase-1 水平显著升高（p<0.001）。此外，血清 Caspase-1 与 AOSD 疾病活动评分（Pouchot 评分，r=0.59，p<0.001）和血清铁蛋白（r=0.54，p<0.001）呈显著正相关。此外，在 AOSD 患者中，血清 Caspase-1 与包括白细胞介素-18 在内的炎症细胞因子之间存在显著相关性。免疫印迹分析在未经治疗的 AOSD 患者的血清中检测到未活化的 Caspase-1（p20）的裂解形式，而在接受免疫抑制治疗的不活动 AOSD 患者的血清中未检测到。
Caspase-1 是 AOSD 诊断和监测的有用生物标志物。Caspase-1 的激活可能与 AOSD 的炎症成分相关，特别是通过炎症小体激活级联反应诱导促炎细胞因子。
