在患有胰腺炎,携带罕见CFTR变异的部分患者中,CFTR功能受损
Dora Angyal1, Karina Kleinfelder2, Fabiana Ciciriello3
1Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, P.O. Box 2040, 3000, CA, Rotterdam, the Netherlands.
概括
囊性纤维化 (CF) 基因变异在一些胰腺炎患者中损害CFTR功能. CFTR调节剂药物显示出改善患者衍生组织中的阴离子运输缺陷的潜力.
科学领域:
- 遗传学和分子生物学
- 胃肠病学 胃肠病学
- 肺部病理学 肺部病理学
背景情况:
- 胰腺炎经常与囊性纤维化 (CF) 基因CFTR的罕见变异有关.
- CFTR编码了一个关键的表皮化物和二碳酸盐通道.
- 了解胰腺炎中CFTR功能对于治疗开发至关重要.
研究的目的:
- 为了研究CFTR变异在胰腺炎患者的功能影响.
- 为了评估CFTR调节剂药物在这个患者队列中的疗效.
主要方法:
- 使用下一代测序识别的CFTR变异.
- 通过汗水测试和鼻腔潜能差异 (NPD) 在体内评估CFTR功能.
- 在直肠活检和来自患者的肠道单层上测量了肠道电流 (ICM).
- 评估化物和碳酸盐的运输,以及对elexacaftor,tezacaftor和ivacaftor (ETI) 组合疗法的反应.
主要成果:
- 三名患有CF致病突变的胰腺炎患者进行了CF典型的功能测试.
- 14名受试者表现出高汗液化物,其中3人暂时被诊断患有CF.
- 在9/17名非CF胰腺炎患者中通过ICM检测出CFTR功能受损,包括那些具有野生型CFTR等位基因的患者.
- 在6/14个单层患者中观察到减少了CFTR依赖的化物运输;在1个患者中,碳酸盐分泌受损.
- 在六个受试者中的四个具有减少化物运输的单层中,ETI改善了CFTR功能.
结论:
- 一部分患有CFTR变异的胰腺炎患者表现出CFTR功能受损.
- 阳离子运输缺陷可能来自CFTR局部外的突变.
- 来自患者的肠道组织和器官对于检测缺陷和评估CFTR调节器功效非常有价值.
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