High Neutrophil Alkaline Phosphatase Activity in Adult-Onset Still's Disease

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.