敏感B细胞受体谱的分析显示,重新填充与风湿性关节炎中对rituximab的临床反应相关
Sabrina Pollastro1,2, Anne Musters1, Giulia Balzaretti1,2
1Department of Clinical Immunology & Rheumatology | Amsterdam Rheumatology & Immunology Centre (ARC), Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
Arthritis research & therapy
|March 17, 2024
概括
B细胞受体 (BCR) 的重新填充,而不是枯竭,预测了与rituximab治疗的类风湿性关节炎 (RA) 患者的缓解. 早期与未变异的BCRs重组与减少的疾病活性相关,这表明B细胞周转率影响治疗反应.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 临床研究 临床研究
背景情况:
- 像Rituximab一样,B细胞消耗疗法对类风湿性关节炎 (RA) 有效,但显示出患者反应的变化.
- 临床结果并不总是与B细胞耗尽的程度相关.
研究的目的:
- 为了前性地分析接受Rituximab治疗的RA患者的B细胞受体 (BCR) 谱.
- 为了确定早期的BCR枯竭或重新填充是否预测临床反应.
- 为了研究BCR曲目动态与疾病活动之间的关系.
主要方法:
- 在28名接受Rituximab治疗的RA患者中分析了周围血液BCR谱.
- 基于不变化的BCR百分比的BCR耗尽和重新填充时间点的定义.
- 对临床反应早期BCR耗尽和重新填充的预测价值的评估.
主要成果:
- 利图西马布治疗改变了BCR谱,增加了克隆扩张和突变负载,从6个月开始逆转.
- 早期BCR耗尽并不能预测早期临床反应,但晚期耗尽与早期反应有关.
- 在治疗后6至12个月间,未发生突变的BCRs的早期重新填充显著降低了疾病活性.
结论:
- 用Rituximab治疗的RA患者的缓解似乎是由未变异BCRs的重新填充驱动的,可能来自天真B细胞,而不是BCR耗尽本身.
- 早期临床效应的个体间差异可能由患者之间B细胞周转率的先前存在的变化来解释.
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