Ding Nana, Ren Haiye, Teng Jialin, Cheng Xiaobing, Ye Junna, Su Yutong, Shi Hui, Hu Qiongyi, Sun Yue, Meng Jianfen, Chi Huihui, Zhou Zhuochao, Jia Jinchao, Yang Chengde, Liu Hong-Lei
Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Rheumatol Ther. 2025 Jun;12(3):513-527. doi: 10.1007/s40744-025-00756-8. Epub 2025 Mar 27.
Adult-onset Still's disease (AOSD) is an autoinflammatory disorder characterized by reactive neutrophilia and dysregulated cytokine release. Mature neutrophils exhibit increased alkaline phosphatase enzyme activity within cytoplasmic granules, particularly in response to inflammation or acute infection. However, whether neutrophil alkaline phosphatase (NAP) activity is elevated in active AOSD, a hyperinflammatory state, remains unclear.
We enrolled 114 patients diagnosed with AOSD, 47 patients with diffuse large B-cell lymphoma (DLBCL), 25 patients with antiphospholipid syndrome (APS), 25 patients with systemic lupus erythematosus (SLE), and 30 healthy controls. Blood samples were collected and smears were prepared, stained, and analyzed to calculate the NAP score.
Our findings demonstrated that NAP scores were significantly elevated in patients with active AOSD compared to those with inactive disease, other rheumatic diseases, and healthy controls (HCs). Further analysis revealed strong positive correlations between the NAP score and white blood cell (WBC) count, neutrophil ratio (NE%), absolute neutrophil count (ANC), ferritin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and systemic disease activity score. Additionally, among patients with AOSD-pre-macrophage activation syndrome (MAS), NAP scores were significantly higher than in those with active AOSD without MAS. Receiver operating characteristic (ROC) curves showed that NAP scores were more effective than other clinical features in distinguishing active AOSD without MAS from patients with AOSD-pre-MAS. Unexpectedly, in patients with AOSD-MAS, NAP scores were significantly reduced compared to those with active AOSD without MAS, likely due to leukopenia.
Our findings revealed that NAP scores were elevated in active AOSD and positively correlated with disease activity.
成人斯蒂尔病（AOSD）是一种自身炎症性疾病，其特征为反应性中性粒细胞增多和细胞因子释放失调。成熟中性粒细胞在细胞质颗粒内表现出碱性磷酸酶活性增加，尤其是对炎症或急性感染的反应。然而，在活动性AOSD（一种高炎症状态）中中性粒细胞碱性磷酸酶（NAP）活性是否升高仍不清楚。
我们纳入了114例诊断为AOSD的患者、47例弥漫性大B细胞淋巴瘤（DLBCL）患者、25例抗磷脂综合征（APS）患者、25例系统性红斑狼疮（SLE）患者和30名健康对照。采集血样并制备涂片，进行染色和分析以计算NAP评分。
我们的研究结果表明，与非活动性疾病患者、其他风湿性疾病患者和健康对照（HCs）相比，活动性AOSD患者的NAP评分显著升高。进一步分析显示，NAP评分与白细胞（WBC）计数、中性粒细胞比例（NE%）、绝对中性粒细胞计数（ANC）、铁蛋白、C反应蛋白（CRP）、红细胞沉降率（ESR）、碱性磷酸酶（ALP）和全身疾病活动评分之间存在强正相关。此外，在AOSD-巨噬细胞活化综合征（MAS）前期患者中，NAP评分显著高于无MAS的活动性AOSD患者。受试者工作特征（ROC）曲线显示，在区分无MAS的活动性AOSD与AOSD-MAS前期患者方面，NAP评分比其他临床特征更有效。出乎意料的是，与无MAS的活动性AOSD患者相比，AOSD-MAS患者的NAP评分显著降低，可能是由于白细胞减少。
我们的研究结果表明，活动性AOSD患者的NAP评分升高，且与疾病活动呈正相关。
