Mass cytometry identifies imbalance of multiple immune-cell subsets associated with biologics treatment in ankylosing spondylitis

IF 2.4 4区医学 Q2 RHEUMATOLOGY

International Journal of Rheumatic Diseases Pub Date : 2024-10-18 DOI:10.1111/1756-185X.15378

Li Lin, Jing Luo, Yue Cai, Xin Wu, Ling Zhou, Ting Li, Xiaobing Wang, Huji Xu

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引用次数: 0

Abstract

Objective

This study aims to comprehensively investigate immune-cell landscapes in ankylosing spondylitis (AS) patients and explore longitudinal immunophenotyping changes induced by biological agents.

Methods

We employed mass cytometry with 35 cellular markers to analyze blood samples from 34 AS patients and 13 healthy controls (HC). Eleven AS patients were re-evaluated 1 month (4 patients) and 3 months (7 patients) after treatment with biological agents. Flow Self-Organizing Maps (FlowSOM) clustering was performed to identify specific cellular metaclusters. We compared cellular abundances across distinct subgroups and validated subset differences using gating strategies in flow cytometry scatter plots, visualized with FlowJo software. The proportions of differential subsets were then used for intercellular and clinical correlation analysis, as well as for constructing diagnostic models based on the random forest algorithm.

Results

In AS patients, we identified and validated nine different immune-cell subsets compared to HC. Three subsets increased: helper T-cell 17 (Th17), mucosa-associated invariant T-cell (MAIT), and classical monocytes (CM). Six subsets decreased: effector memory T-cell (TEM), naïve B cells, transitional B cells, IL10+ memory B cells, non-classical monocytes (NCM), and neutrophils. Treatments with biological agents could rectify cellular abnormalities, particularly the imbalance of CM/NCM. Furthermore, these subsets may serve as biomarkers for assessing disease activity and constructing effective diagnostic models for AS.

Conclusion

These findings provide novel insights into the specific patterns of immune cell in AS, facilitating the further development of novel biomarkers and potential therapeutic targets for AS patients.

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质控细胞仪发现强直性脊柱炎患者的多种免疫细胞亚群失衡与生物制剂治疗有关

目的本研究旨在全面调查强直性脊柱炎（AS）患者的免疫细胞景观，并探讨生物制剂诱导的纵向免疫表型变化。方法我们采用含有 35 种细胞标记物的质谱仪分析了 34 名强直性脊柱炎患者和 13 名健康对照者（HC）的血液样本。在使用生物制剂治疗 1 个月（4 名患者）和 3 个月（7 名患者）后，对 11 名 AS 患者进行了重新评估。我们进行了流式自组织图（FlowSOM）聚类，以确定特定的细胞元簇。我们比较了不同亚群的细胞丰度，并使用流式细胞仪散点图中的门控策略验证了亚群差异，该散点图用FlowJo软件进行了可视化。然后将差异亚组的比例用于细胞间和临床相关性分析，并根据随机森林算法构建诊断模型。结果在强直性脊柱炎患者中，与 HC 相比，我们发现并验证了九种不同的免疫细胞亚群。三个亚群增加了：辅助性 T 细胞 17（Th17）、粘膜相关不变 T 细胞（MAIT）和经典单核细胞（CM）。六个亚群减少：效应记忆 T 细胞（TEM）、幼稚 B 细胞、过渡 B 细胞、IL10+ 记忆 B 细胞、非典型单核细胞（NCM）和中性粒细胞。使用生物制剂治疗可纠正细胞异常，尤其是 CM/NCM 的失衡。此外，这些亚群可作为评估疾病活动性和构建强直性脊柱炎有效诊断模型的生物标志物。结论这些研究结果为了解强直性脊柱炎免疫细胞的特定模式提供了新的视角，有助于进一步为强直性脊柱炎患者开发新的生物标志物和潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Rheumatic Diseases RHEUMATOLOGY-

CiteScore

3.70

自引率

4.00%

发文量

362

审稿时长

1 months

期刊介绍： The International Journal of Rheumatic Diseases (formerly APLAR Journal of Rheumatology) is the official journal of the Asia Pacific League of Associations for Rheumatology. The Journal accepts original articles on clinical or experimental research pertinent to the rheumatic diseases, work on connective tissue diseases and other immune and allergic disorders. The acceptance criteria for all papers are the quality and originality of the research and its significance to our readership. Except where otherwise stated, manuscripts are peer reviewed by two anonymous reviewers and the Editor.