AOSD endotypes based on immune cell profiles: patient stratification with hierarchical clustering analysis

OBJECTIVES: This study aimed to analyse the immune cell profiles of adult-onset Still's disease (AOSD) and to stratify disease-associated endotypes. METHODS: We included 95 cases of treatment-naïve patients with AOSD and 66 cases of healthy controls. Patients with AOSD were classified via an unbiased hierarchical cluster analysis based on circulating immune cells. Their clinical and laboratory characteristics, treatment management, systemic scores and outcomes were then analysed. RESULTS: The proportions of neutrophils and CD8+ T cells were significantly higher while monocytes and natural killer and CD4+ T cells were decreased in patients with AOSD (all P < 0.005). Unbiased hierarchical cluster analysis classified 95 AOSD into three endotype-based groups: group 1 had the highest percentage of neutrophils (neu-dominant group), group 2 had the highest percentage of monocytes (mono-dominant group) and group 3 had the highest percentage of CD8+ T cells (CD8-dominant group). Patients in group 3 had the highest systemic score at diagnosis and were more likely to have pulmonary infiltrates, pericarditis, splenomegaly and poorer treatment responses. A correlation study revealed that the CD4 to CD8 ratio was negatively correlated with the systemic score and positively correlated with treatment response in patients with AOSD (P = 0.001 and P = 0.0091). During the 24.6 (15.2) months of follow-up, the highest total number of disease flares occurred in group 3 (P < 0.0001). CONCLUSION: Hierarchical cluster analysis of peripheral immune cells classified AOSD into three disease-related endotypes. Group 3 showed higher systemic score and poorer treatment responses.