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AOSD Endotypes based on immune cell profiles: patient stratification with hierarchical clustering analysis
Rheumatology ( IF 5.5 ) Pub Date : 2022-08-16 , DOI: 10.1093/rheumatology/keac439
Ruru Guo 1 , Xuesong Liu 1, 2 , Yixuan Li 1 , Xinyu Meng 1 , Rui Li 1 , Xiaoxiang Chen 1 , Liangjing Lu 1
Affiliation  

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 (HCs). 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.

中文翻译:

基于免疫细胞谱的 AOSD 内型:通过层次聚类分析对患者进行分层

目的 本研究旨在分析成人斯蒂尔病 (AOSD) 的免疫细胞谱并对疾病相关的内型进行分层。方法 我们纳入了 95 例 AOSD 初治患者和 66 例健康对照 (HC)。通过基于循环免疫细胞的无偏层次聚类分析对 AOSD 患者进行分类。然后分析了他们的临床和实验室特征、治疗管理、系统评分和结果。结果 AOSD 患者中性粒细胞和 CD8+ T 细胞的比例显着升高,而单核细胞和自然杀伤细胞和 CD4+ T 细胞减少(均 p < 0.005)。无偏层次聚类分析将 95 个 AOSD 分为三个基于内型的组:第 1 组中性粒细胞百分比最高(Neu 显性组),第 2 组的单核细胞百分比最高(单核显性组),第 3 组的 CD8+ T 细胞百分比最高(CD8 显性组)。第 3 组患者在诊断时具有最高的系统评分,并且更有可能出现肺部浸润、心包炎、脾肿大和较差的治疗反应。一项相关性研究表明,CD4 与 CD8 的比率与系统评分呈负相关,与 AOSD 患者的治疗反应呈正相关(p = 0.001 和 p = 0.0091)。在 24.6 ± 15.2 个月的随访期间,第 3 组的疾病发作总数最多 (p < 0.0001)。结论 外周免疫细胞的层次聚类分析将 AOSD 分为三种与疾病相关的内型。第 3 组表现出更高的系统评分和更差的治疗反应。
更新日期:2022-08-16
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