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活化的幼稚自身反应性 B 细胞的扩增及其与系统性红斑狼疮患者疾病活动的关系。

The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients.

机构信息

Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon Sai 4 Road, Salaya, Nakhonpathom, 73170, Thailand.

Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Ratchathewi, Bangkok, 10400, Thailand.

出版信息

Arthritis Res Ther. 2021 Jul 6;23(1):179. doi: 10.1186/s13075-021-02557-0.

Abstract

BACKGROUND

Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis.

METHODS

Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients' peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells.

RESULTS

The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells.

CONCLUSION

Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

摘要

背景

自身反应性 B 细胞被认为是系统性红斑狼疮(SLE)发病机制中的关键参与者。然而,由于其 B 细胞异质性,阐明产生抗 dsDNA 抗体的特定 B 细胞亚群受到限制。本研究旨在鉴定显示对 DNA 自身反应性并有助于狼疮发病机制的外周 B 细胞亚群。

方法

流式细胞术用于检测 SLE 患者外周血中的总 B 细胞亚群(n=20)和 DNA 自身反应性 B 细胞(n=15)。使用改良的 SLEDAI-2K 评估 SLE 患者的临床疾病活动,并与扩展的 B 细胞亚群和 DNA 自身反应性 B 细胞进行相关性分析。

结果

在 SLE 患者中观察到循环双阴性 2(DN2)和激活的幼稚(aNAV)B 细胞的增加。扩展的 B 细胞亚群和 DNA 自身反应性 B 细胞代表了 aNAV B 细胞的高比例,其 CD69 和 CD86 过度表达。aNAV B 细胞在总 B 细胞群体中的频率与改良的 SLEDAI-2K 评分显著相关。进一步分析表明,aNAV DNA 自身反应性 B 细胞的扩增与疾病活动和血清抗 dsDNA 抗体水平更相关,而与总 aNAV B 细胞无关。

结论

我们的研究表明 SLE 患者中存在 aNAV B 细胞的扩增。aNAV B 细胞的频率与疾病活动患者之间的关联表明这些扩增的 B 细胞可能在 SLE 的发病机制中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3556/8259008/a9bbcab23a7d/13075_2021_2557_Fig1_HTML.jpg

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