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阿尼鲁单抗可减轻系统性红斑狼疮患者的滤泡辅助性T细胞活化。

Anifrolumab Attenuates Follicular Helper T Cell Activation in Patients with Systemic Lupus Erythematosus.

作者信息

Diós Ádám, Gyetvai Ágnes, Papp Gábor, Tarr Tünde

机构信息

Division of Clinical Immunology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.

出版信息

Int J Mol Sci. 2025 Jul 31;26(15):7397. doi: 10.3390/ijms26157397.

Abstract

Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects of inhibited type I IFN signaling on circulating follicular helper T subsets (T), follicular regulatory T cells (T), and B lymphocyte subpopulations, reflecting the ongoing germinal center reactions in SLE patients. Peripheral blood samples were obtained from ten SLE patients before the initiation of anifrolumab treatment, and at months 6 and 12 of the intervention period. Flow cytometry analysis was performed to assess the frequencies of circulating T cell subsets, T cells, and certain B cell subpopulations. Serological parameters, including autoantibody levels and complement components, were determined as part of the routine diagnostic evaluation. We observed a significant and sustained reduction in the percentage of activated circulating T cells. Notably, the frequency of CXCR3CCR6 T17 cells decreased, whereas the proportion of CXCR3CCR6 T1 cells increased significantly. Furthermore, the proportion of the IgDCD27 double-negative B lymphocytes was also significantly reduced. These findings suggest that anifrolumab therapy attenuates T cell activation, which may contribute to its clinical efficacy by modulating germinal center responses in SLE.

摘要

系统性红斑狼疮(SLE)是一种严重的自身免疫性疾病,其特征为自身抗体产生和多器官受累。阿尼鲁单抗是一种靶向I型干扰素(IFN)受体的单克隆抗体,已被批准用于治疗SLE。我们的目的是研究抑制I型IFN信号传导对循环滤泡辅助性T细胞亚群(Tfh)、滤泡调节性T细胞(Tfr)和B淋巴细胞亚群的长期影响,以反映SLE患者中正在进行的生发中心反应。在开始阿尼鲁单抗治疗前以及干预期的第6个月和第12个月,从10例SLE患者中采集外周血样本。进行流式细胞术分析以评估循环T细胞亚群、Tfr细胞和某些B细胞亚群的频率。作为常规诊断评估的一部分,测定了包括自身抗体水平和补体成分在内的血清学参数。我们观察到活化循环Tfh细胞的百分比显著且持续降低。值得注意的是,CXCR3+CCR6+ T17细胞的频率降低,而CXCR3+CCR6- T1细胞的比例显著增加。此外,IgD-CD27双阴性B淋巴细胞的比例也显著降低。这些发现表明,阿尼鲁单抗治疗可减轻Tfh细胞活化,这可能通过调节SLE中的生发中心反应而有助于其临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d12/12347037/07b8f6b7a60a/ijms-26-07397-g001.jpg

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