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

IF 4.6 2区 医学 Q1 Medicine
Xiaowei Chen, Lingzhen Hu, Lingxiao Zhu, Jianxin Tu, Jiajun Gui, Mengyuan Fang, Li Sun
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Abstract

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. 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. 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). 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. Chineses Clinical Trials Registry; https://www.chictr.org.cn ; ChiCTR2400086874.
泰利他赛普治疗系统性红斑狼疮后B细胞亚群动力学的前瞻性分析
系统性红斑狼疮(SLE)是一种以B细胞活化和自身抗体形成为特征的自身免疫性炎症性疾病。Telitacicept是B细胞通路的双重抑制剂,可中和来自B淋巴细胞刺激剂和增殖诱导配体的信号。本研究的目的是探讨替利他赛普治疗后SLE患者详细B细胞亚群的变化。纳入20例活动性SLE患者(SLEDAI-2 K≥6),在开始Telitacicept治疗后0,4,12和24周进行B细胞亚群分析和临床评估。此外,还测量了21名健康对照者的B细胞亚群。流式细胞术定量B细胞亚群。治疗6个月后,记录到95%(19/20)的SRI-4缓解率和35%(7/20)的LLDAS达到。与基线相比,SLEDAI-2 K评分和抗dsdna水平显著降低(均p < 0.001),补体C3和C4水平增加(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(p < 0.05)、移行B细胞、初代B细胞和短寿命浆细胞(p < 0.01)减少。B调节性细胞(Breg)比例升高(p < 0.05)。泰利他塞普联合标准治疗可显著改变SLE患者的B细胞亚群和临床标志物。初始和过渡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。中国临床试验注册;https://www.chictr.org.cn;ChiCTR2400086874。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.60
自引率
2.00%
发文量
261
审稿时长
14 weeks
期刊介绍: Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.
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