Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; The Royal London Hospital, Barts Health NHS Trust, London, UK.
Clin Immunol. 2024 Dec;269:110380. doi: 10.1016/j.clim.2024.110380. Epub 2024 Oct 18.
Recent studies demonstrate the efficacy of B cell-targeting therapies in managing multiple sclerosis (MS) activity, emphasizing the critical role of B cells in MS pathogenesis. CladB study aimed to quantify the temporal changes in peripheral immune cells and their activity over 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS). Ten participants (3 males, 7 females) had blood samples collected at multiple intervals (Day 0, 1, 5, then weekly for 8 weeks, biweekly for up to 24 weeks, and monthly for up to 96 weeks) for immune cell analysis, compared to a historical alemtuzumab-treated cohort. Paired cerebrospinal fluid (CSF) was also taken for various analyses, alongside clinical and brain imaging assessments. CladT depleted memory B cells, while alemtuzumab rapidly depleted T and B cells. The кFLC index decreased from 164.5 ± 227.1 to 71.3 ± 84.7 at 48 weeks (p = 0.002) and to 64.4 ± 67.3 at 96 weeks (p = 0.01). The IgG index dropped from 1.1 ± 0.5 at baseline to 0.8 ± 0.4 at 48 weeks (p = 0.014) and to 0.8 ± 0.3 at 96 weeks (p = 0.02). CSF CXCL-13 decreased from 88.6 ± 68.4 pg/mL to 39.4 ± 35.2 pg/mL at 48 weeks (p = 0.037) and 19.1 ± 11.7 pg/mL at 96 weeks (p = 0.027). CSF NfL levels were reduced at 48 weeks (p = 0.01). CladT primarily depletes memory B cells and antibody-secreting cell precursors in RRMS, leading to sustained effects on intrathecal antibody production and total IgG, and a reduction in CSF CXCL-13.
最近的研究表明，B 细胞靶向疗法在多发性硬化症（MS）活动管理中具有疗效，强调了 B 细胞在 MS 发病机制中的关键作用。CladB 研究旨在量化克拉屈滨片（CladT）治疗复发缓解型多发性硬化症（RRMS） 96 周期间外周免疫细胞及其活性的时间变化。10 名参与者（3 名男性，7 名女性）在多个时间点（第 0、1、5 天，然后每周一次持续 8 周，每两周一次持续 24 周，每月一次持续 96 周）采集血液样本进行免疫细胞分析，与历史上接受阿仑单抗治疗的队列进行比较。还采集配对的脑脊液（CSF）进行各种分析，同时进行临床和脑成像评估。CladT 耗尽记忆 B 细胞，而阿仑单抗迅速耗尽 T 和 B 细胞。κFLC 指数从 48 周时的 164.5±227.1 降至 71.3±84.7（p=0.002），并在 96 周时降至 64.4±67.3（p=0.01）。IgG 指数从基线时的 1.1±0.5 降至 48 周时的 0.8±0.4（p=0.014）和 96 周时的 0.8±0.3（p=0.02）。CSF CXCL-13 从 88.6±68.4pg/mL 降至 48 周时的 39.4±35.2pg/mL（p=0.037）和 96 周时的 19.1±11.7pg/mL（p=0.027）。CSF NfL 水平在 48 周时降低（p=0.01）。CladT 主要在 RRMS 中耗尽记忆 B 细胞和抗体分泌细胞前体，导致鞘内抗体产生和总 IgG 的持续效应，以及 CSF CXCL-13 的减少。
