RT期刊文章SR电子T1修正雌性生殖道功能肠道瀑样指导治疗囊性纤维化摩根富林明欧洲呼吸杂志乔和J FD欧元欧洲呼吸学会SP 1902426 10.1183/13993003.02426 -2019签证官57是1 A1 Ramalho, Anabela s A1 Furstova,伊娃A1 Vonk, Annelotte m . A1费,188bet官网地址Marc A1 Verfaillie Catherine A1 Dupont Lieven A1 Boon miieke A1 Proesmans Marijke A1 Beekman Jeffrey M. A1 Sarouk Ifat A1 Vazquez Cordero Carlos A1 Vermeulen Francois A1 De Boeck鉴于囊性纤维化跨膜电导调节(CFTR)突变的数量巨大，囊性纤维化(CF)患者需要预测CFTR调节治疗获益的生物标志物。目的研究CFTR常见突变和罕见突变患者的CFTR功能，并评估CFTR功能与临床资料的相关性。方法从97名CF患者的直肠活检中培养出肠道类器官。通过定量forskolin诱导的类器官肿胀和定量CFTR校正器、增强器及它们的组合诱导的类器官肿胀来测量CFTR残余功能。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，残余CFTR功能与汗液氯化物值相关(r2=0.87)。当研究相同基因型时，CFTR调节因子在类器官中的作用与临床试验报告的肺功能(r2=0.90)和汗液氯化物(r2=0.95)的平均改善密切相关。我们确定了调节剂治疗的候选基因型，如E92K、Q237E、R334W和L159S。基于类器官的结果，两名受试者开始了调节性治疗:一名纯合复杂等位基因Q359K_T360K，另一名突变为E60K。两个实验对象都有重要的临床益处。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