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滤泡辅助性 T 细胞在利妥昔单抗治疗天疱疮患者临床缓解和复发中的作用。

The Role of T Follicular Helper Cells in Clinical Remission and Relapse in Patients with Pemphigus Treated with Rituximab.

机构信息

Prof. Ayşe Akman Karakaş, MD, Akdeniz Univercity Pınarbaşı, Akdeniz Ünv., 07070 Konyaaltı/Antalya, Antalya, Turkey;

出版信息

Acta Dermatovenerol Croat. 2023 Nov;31(2):72-79.

PMID:38006366
Abstract

BACKGROUND

Pemphigus is a rare chronic autoimmune disease. Recent studies have found that T follicular helper (Tfh) cells may play a role in autoimmune diseases. In this study, Tfh cells frequency, BCL6 gene expression, IL-21, and IL-6 cytokines levels were examined, with the aim of understanding the effect of RTX on these cells in the onset of clinical remission or relapse in patients with pemphigus.

METHODS

20 patients with pemphigus vulgaris and 20 healthy controls without any autoimmune diseases that were admitted to the Dermatology and Venereology Clinic of the Akdeniz University Hospital were included. Peripheral blood sample was taken from all individuals and studied to analyze Tfh cell distribution, IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes with flow cytometry, plasma IL-21 levels with ELISA, and mRNA levels that refer to BCL6 expression with PCR.

RESULTS

Circulating Tfh cell distribution and IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes and mRNA levels that refer to BCL6 expression showed no difference between patient and control groups. However, in patients who had received rituximab treatment there was a significant reduction in Tfh cells compared with other groups. Plasma IL-21 levels were significantly higher in the patient group.

CONCLUSIONS

We found that plasma concentrations of the cytokine IL-21 were greatly increased in the pemphigus compared with the control group. There were no significant differences in Tfh cell percentages between the patient and control groups. Tfh cells were decreased in patients who received rituximab treatment. Our findings show that the response to RTX in pemphigus causes a reduction in circulating T follicular helper cells, but not in the plasma IL-21 level. Further studies are required to clarify the role of Tfh cells in pemphigus vulgaris.

摘要

背景

天疱疮是一种罕见的慢性自身免疫性疾病。最近的研究发现,滤泡辅助性 T 细胞(Tfh)可能在自身免疫性疾病中发挥作用。本研究检测了 Tfh 细胞频率、BCL6 基因表达、IL-21 和 IL-6 细胞因子水平,旨在了解 RTX 对天疱疮患者临床缓解或复发时这些细胞的影响。

方法

纳入了 20 例天疱疮患者和 20 例无任何自身免疫性疾病的阿克登兹大学医院皮肤科和性病科的健康对照者。从所有个体采集外周血样并进行分析,通过流式细胞术分析 Tfh 细胞分布、CD3+CD4+CXCR5+淋巴细胞中 IL-21 和 IL-6 分布,用 ELISA 检测血浆 IL-21 水平,用 PCR 检测 BCL6 表达的 mRNA 水平。

结果

患者组和对照组之间循环 Tfh 细胞分布以及 CD3+CD4+CXCR5+淋巴细胞中 IL-21 和 IL-6 分布和 BCL6 表达的 mRNA 水平没有差异。然而,与其他组相比,接受利妥昔单抗治疗的患者 Tfh 细胞显著减少。患者组的血浆 IL-21 水平显著升高。

结论

我们发现天疱疮患者的细胞因子 IL-21 血浆浓度明显高于对照组。患者组和对照组之间 Tfh 细胞百分比没有显著差异。接受利妥昔单抗治疗的患者 Tfh 细胞减少。我们的研究结果表明,天疱疮对 RTX 的反应导致循环 T 滤泡辅助细胞减少,但血浆 IL-21 水平没有变化。需要进一步的研究来阐明 Tfh 细胞在天疱疮中的作用。

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引用本文的文献

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Healthy individuals genetically at-risk for the development of Pemphigus vulgaris or Alopecia areata share disease-like cytokine dysregulation.在基因上有寻常型天疱疮或斑秃发病风险的健康个体存在类似疾病的细胞因子失调。
Front Immunol. 2025 Jan 13;15:1500284. doi: 10.3389/fimmu.2024.1500284. eCollection 2024.
2
Cytokine profiling reveals HLA-linked Th2 and Th17 driven immune activation in pemphigus vulgaris patients and genetically susceptible healthy controls.细胞因子谱分析揭示寻常型天疱疮患者及遗传易感性健康对照中HLA相关的Th2和Th17驱动的免疫激活。
Front Immunol. 2024 Dec 4;15:1500231. doi: 10.3389/fimmu.2024.1500231. eCollection 2024.