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基于免疫细胞图谱的成人斯蒂尔病内型:采用层次聚类分析进行患者分层

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

作者信息

Guo Ruru, Liu Xuesong, Li Yixuan, Meng Xinyu, Li Rui, Chen Xiaoxiang, Lu Liangjing

机构信息

Department of Rheumatology.

Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P. R. China.

出版信息

Rheumatology (Oxford). 2023 Apr 3;62(4):1636-1644. doi: 10.1093/rheumatology/keac439.

DOI:10.1093/rheumatology/keac439
PMID:35972374
Abstract

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.

摘要

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例未经治疗的AOSD患者和66例健康对照。基于循环免疫细胞,通过无偏层次聚类分析对AOSD患者进行分类。然后分析他们的临床和实验室特征、治疗管理、全身评分及预后。

结果

AOSD患者中性粒细胞和CD8⁺T细胞比例显著升高,而单核细胞、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例AOSD患者分为三个基于内型的组:第1组中性粒细胞百分比最高(中性粒细胞主导组),第本组单核细胞百分比最高(单核细胞主导组),第3组CD8⁺T细胞百分比最高(CD8主导组)。第3组患者诊断时全身评分最高,更易出现肺部浸润、心包炎、脾肿大且治疗反应较差。相关性研究显示,AOSD患者CD4与CD8比值与全身评分呈负相关,与治疗反应呈正相关(P = 0.001和P = 0.0091)。在24.

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