TY -的T1 -修正的雌性生殖道功能肠道瀑样指导治疗囊性纤维化JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02426 -2019欧元六世- 57 - 1 SP - 1902426 AU Ramalho Anabela s . AU - Furstova Eva盟——Vonk Annelotte m . AU -费,马克•AU - Verfaillie凯瑟琳盟——杜邦公司,Lieven AU - Boon, Mieke AU - Proesmans, Marijke AU - Beekman, Jeffrey M. AU - Sarouk, Ifat AU - Vazquez Cordero, Carlos AU - Vermeulen, Francois AU - De Boeck, Kris A2 -，考虑到囊性纤维化跨膜传导调节因子(CFTR)的大量突变，囊性纤维化(CF)患者需要生物标志物来预测CFTR调节疗法的疗效。目的研究常见和罕见CFTR突变患者的类器官CFTR功能，并评价CFTR功能与临床资料的相关性。方法从97例CF患者的直肠活检标本中培养出肠道类器官，通过定量forskolin诱导的类器官肿胀来测定残余CFTR功能，通过定量CFTR校正器、增强器及其联合诱导的类器官肿胀来测定调节剂对CFTR校正器、增强器及其联合诱导的类器官肿胀的反应。类器官资料与文献中的临床资料相关。结果在28个基因型中，剩余CFTR功能与汗氯值相关(r2=0.87)。在研究相同基因型时，临床试验中报道的CFTR调节因子在类器官中拯救CFTR功能与肺功能(r2=0.90)和汗氯(r2=0.95)的平均改善密切相关。我们确定了调节治疗的候选基因型，如E92K、Q237E、R334W和L159S。基于类器官结果，两名受试者开始了调制剂治疗:一名为复杂等位基因Q359K_T360K纯合，另一名为E60K突变。两组受试者均有重大临床获益。Conclusions Measurements of residual CFTR function and rescue of function by CFTR modulators in intestinal organoids correlate closely with clinical data. Our results for reference genotypes concur with previous results. CFTR function measured in organoids can be used to guide precision medicine in patients with CF, positioning organoids as a potential in vitro model to bring treatment to patients carrying rare CFTR mutations.Rescue of CFTR function with modulators measured in colon organoids can be used to guide precision medicine in patients with cystic fibrosis. Organoids are an effective model to bring treatment to patients with CF carrying rare CFTR mutations. https://bit.ly/2VHHH6s ER -