在患有囊性纤维化同胞性F508del患者中,患者产生的肠道器官与CFTR调节剂的临床反应之间的相关性
Noelia Rodriguez Mier1, Senne Cuyx1, Kris De Boeck1
1Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium; Department of Pediatrics, Pediatric Pulmonology, University Hospital Leuven, Leuven, Belgium.
概括
在囊性纤维化 (CF) 患者中,来自患者的肠道器官 (PDIO) 显示出可变的临床反应预测. 然而,PDIO响应的大小与CFTR调节器治疗后的汗水化物和肺功能改善相关.
科学领域:
- 生物医学研究
- 遗传学和基因组学
- 肺部医学
背景情况:
- 患者衍生肠道器官 (PDIO) 用于预测囊性纤维化外膜导电调节器 (CFTR) 响应.
- 尽管基因型相关,但对CFTR调节剂的个体反应在F508del同卵性PwCF之间存在差异.
- 这项研究专门评估了F508del同卵性群体内的PDIO反应相关性.
研究的目的:
- 评估使用CFTR调节剂治疗的F508del同卵性pwCF的PDIO反应与临床结果之间的相关性.
- 调查基因变异 (CFTR SNPs) 或基因表达 (转录组学) 是否解释了反应中的表型变异性.
- 确定PDIOs作为CFTR调节器功效的预测生物标志物的有用性.
主要方法:
- 对60个F508del同卵性pwCF进行了回顾性多中心研究.
- 根据福斯科林诱导的胀 (FIS) 测定,选择对tezacaftor/ivacaftor (TI) 和elexacaftor/tezacaftor/ivacaftor (ETI) 的最高和最低PDIO反应者.
- 在治疗前和治疗后测量临床结果 (SCC,精神测量,BMI,恶化,静脉抗生素使用).
- 在高响应者和低响应者中分析CFTRSNP和转录组学.
主要成果:
- 在治疗后,高PDIO和低PDIO响应组之间没有显著的临床结果差异.
- 与TI相比,ETI的PDIO反应显著更高.
- 当结合TI和ETI数据时,PDIO反应大小与汗液化物度 (SCC) 和ppFEV1的改善有很强的相关性.
- 在响应组之间没有发现CFTRSNP或转录组的差异.
结论:
- 虽然PDIO响应组没有单独预测临床结果,但PDIO响应的大小是临床益处的重要预测指标.
- PDIO反应大小与SCC和ppFEV1的变化有很强的关联,支持其作为预测生物标志物的潜力.
- 在F508del同卵性pwCF中,通过考虑PDIO响应的大小和遗传因素,可以提高CFTR调节器功效的预测.
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