持久的古典和非典型记忆B细胞是ocrelizumab治疗多发性硬化症患者异质疫苗反应的基础
Ryan Curtin1,2, Yogambigai Velmurugu1,2, Fatoumatta Dibba1,2
1New York University (NYU) Grossman School of Medicine, New York, NY, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
接受ocrelizumab (OCR) 治疗的患者对mRNA疫苗的反应各异. 持久性记忆B细胞,没有被OCR耗尽,是多发性硬化症患者有效接种疫苗的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 疫苗学 疫苗学 疫苗学
背景情况:
- 多发性硬化症患者接受B细胞消耗疗法ocrelizumab (OCR) 治疗,在SARS-CoV-2mRNA疫苗接种后表现出不一致的幽默免疫力.
- 驱动这种反应异质性的潜在免疫机制尚未完全理解.
研究的目的:
- 纵向分析OCR治疗多发性硬化症患者和疫苗接种后健康对照的抗原特异性T和B细胞反应.
- 在接受OCR治疗的患者中,确定与幽默反应结果相关的免疫细胞组成和动态.
主要方法:
- 在SARS-CoV-2 mRNA疫苗接种后对T和B细胞反应的纵向分析.
- 将多发性硬化症患者分为"超级响应者" (SR),"响应者" (R) 和"不响应者" (NR) 的分类,基于抗尖峰IgG标位.
- 流细胞计,以评估免疫细胞种群,包括特定的B细胞子集.
主要成果:
- 在所有接受OCR治疗的患者中,CD4+和CD8+T细胞种群总体保持稳定.
- 不同的B细胞组成使得响应者与不响应者有所区别.
- 特定的记忆B细胞子集 (CD19+CD27+经典记忆B细胞和CD19+CD27-IgD-T-bet+CD11c+CXCR5-DN2样B细胞) 在OCR后持续存在,并且在SR患者中比NR患者更为丰富.
结论:
- 持久性记忆B细胞子集,耐受于ocrelizumab耗尽,是多发性硬化症患者疫苗反应的关键免疫相关物.
- 这些有弹性的B细胞群可以作为疫苗疗效的机制调解者.
- 识别这些B细胞子集为接受B细胞消耗疗法的患者提供了潜在的治疗点,以提高疫苗的有效性.
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