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红斑狼疮患者在 flares 前后的 T 外周辅助和 T 滤泡辅助亚群的纵向分析。

Longitudinal analysis at pre- and post-flare of T peripheral helper and T follicular helper subsets in patients with systemic lupus erythematosus.

机构信息

Innovative Research division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

出版信息

Immunol Lett. 2024 Oct;269:106905. doi: 10.1016/j.imlet.2024.106905. Epub 2024 Aug 3.

Abstract

OBJECTIVE

We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare.

METHODS

This study included inactive (n = 29) and active (n = 55) patients with SLE. Tph subsets, Tfh subsets, CD11c B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array.

RESULTS

Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare.

CONCLUSION

Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.

摘要

目的

我们旨在分析狼疮低疾病活动状态(LLDAS)下狼疮患者在疾病发作前外周辅助性 T 细胞(Tph)和循环滤泡辅助性 T 细胞(Tfh)的时间变化过程。

方法

本研究纳入了 29 名无活动期和 55 名活动期的系统性红斑狼疮(SLE)患者。通过流式细胞术检测 Tph 亚群、Tfh 亚群、血液中的 CD11c B 细胞和浆细胞。通过电化学发光法或细胞因子珠阵列检测干扰素(IFNs)等细胞因子的血液水平。

结果

与无活动期患者相比,活动期 SLE 患者表现出 Tph1、Tph2、Tfh1 和 Tfh2 亚群的频率增加,但其他亚群没有明显变化。在药物治疗期间,Tph1、Tph2 和 Tfh2 亚群随着疾病活动度的降低而显著减少,Tph1 和 Tph2 亚群与 SLE 疾病活动指数(SLEDAI)呈正相关。对疾病发作前后患者的时间过程分析显示,在疾病发作前处于 LLDAS 的患者中,Tph 亚群和 Tfh 亚群水平相对较低。在发作时,Tph 细胞,特别是 Tph1 和 Tph2 亚群增加,与 SLEDAI 相关。此外,在疾病发作前处于 LLDAS 的患者中,IFN-α2a、IFN-γ 和 IFN-λ1 的血液水平较低,但随着疾病发作,这些 IFN,特别是 IFN-λ1,水平升高。

结论

Tph1 和 Tph2 亚群频率增加和血清 IFN-λ1 水平升高可能是 SLE 发作的关键因素。

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