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泰它西普治疗系统性红斑狼疮后B细胞亚群动态变化的前瞻性分析

Prospective analysis of B cell subset dynamics following telitacicept treatment in systemic lupus erythematosus.

作者信息

Chen Xiaowei, Hu Lingzhen, Zhu Lingxiao, Tu Jianxin, Gui Jiajun, Fang Mengyuan, Sun Li

机构信息

Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Alley, Wenzhou, 325000, People's Republic of China.

Department of Rheumatology, Jinhua Municipal Central Hospital, Jinhua, People's Republic of China.

出版信息

Arthritis Res Ther. 2025 Jun 18;27(1):126. doi: 10.1186/s13075-025-03584-x.

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease marked by B cell activation and autoantibody formation. Telitacicept, a dual inhibitor of the B cell pathway, neutralizes signals from B lymphocyte stimulator and a proliferation-inducing ligand. The aim of this study is to investigate the changes in detailed B cell subsets in SLE patients following Telitacicept treatment.

METHODS

Twenty active SLE patients (SLEDAI-2 K ≥ 6) were enrolled, with B cell subsets analyses and clinical assessments conducted at 0, 4, 12, and 24 weeks after initiating Telitacicept treatment. Additionally, B cell subsets were measured in 21 healthy controls. Flow cytometry was used to quantify B cell subsets.

RESULTS

After six months of treatment, a 95% (19/20) SRI-4 response rate and a 35% (7/20) achievement of LLDAS were recorded. Compared to baseline, there were significant reductions in SLEDAI-2 K scores and anti-dsDNA levels (both p < 0.001), along with increases in complement C3 and C4 levels (both p < 0.001). Additionally, there was a significant decrease in 24-h urine protein levels (p = 0.004). B cell subset analysis revealed decreases in total B cells (p < 0.05), transitional B cells, naive B cells, and short-lived plasma cells (all p < 0.01). The proportion of B regulatory (Breg) cell increased (p < 0.05).

CONCLUSION

Combining telitacicept with standard therapy induced significant changes in B cell subsets and clinical markers in SLE patients. The reduction in naive and transitional B cells, along with the restoration of Breg cell, suggests a potential positive influence on immunoregulatory capacity.

TRIAL REGISTRATION

Chineses Clinical Trials Registry; https://www.chictr.org.cn ; ChiCTR2400086874.

摘要

背景

系统性红斑狼疮(SLE)是一种自身免疫性炎症性疾病,其特征为B细胞活化和自身抗体形成。泰它西普是一种B细胞途径双抑制剂,可中和来自B淋巴细胞刺激因子和增殖诱导配体的信号。本研究旨在调查泰它西普治疗后SLE患者详细B细胞亚群的变化。

方法

纳入20例活动性SLE患者(SLEDAI-2K≥6),在开始泰它西普治疗后的0、4、12和24周进行B细胞亚群分析和临床评估。此外,对21名健康对照者进行了B细胞亚群检测。采用流式细胞术对B细胞亚群进行定量分析。

结果

治疗6个月后,SRI-4反应率为95%(19/20),达到LLDAS的比例为35%(7/20)。与基线相比,SLEDAI-2K评分和抗双链DNA水平显著降低(均p<0.001),补体C3和C4水平升高(均p<0.001)。此外,24小时尿蛋白水平显著降低(p=0.004)。B细胞亚群分析显示,总B细胞、过渡性B细胞、幼稚B细胞和短寿命浆细胞均减少(均p<0.01)。B调节(Breg)细胞比例增加(p<0.05)。

结论

泰它西普与标准治疗联合应用可使SLE患者的B细胞亚群和临床指标发生显著变化。幼稚和过渡性B细胞的减少以及Breg细胞的恢复表明对免疫调节能力有潜在的积极影响。

试验注册

中国临床试验注册中心;https://www.chictr.org.cn;ChiCTR2400086874。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d689/12175369/66391c815aa6/13075_2025_3584_Fig1_HTML.jpg

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