直肠器官形态分析（ROMA）作为囊性纤维化诊断分类的新生理测定
Rectal organoid morphology analysis (ROMA) as a novel physiological assay for diagnostic classification in cystic fibrosis
影响因子:7.70000
分区:医学1区 Top / 呼吸系统2区
发表日期:2024 Aug 19
作者:
Senne Cuyx, Anabela Santo Ramalho, Steffen Fieuws, Nikky Corthout, Marijke Proesmans, Mieke Boon, Kaline Arnauts, Marianne S Carlon, Sebastian Munck, Lieven Dupont, Kris De Boeck, François Vermeulen,
摘要
诊断囊性纤维化（CF）并不总是直接的，尤其是当汗水氯化物浓度（SCC）中间且识别出<2 CF引起的CFTR变体时。指南中提出的生理CFTR分析，鼻电势差和肠电流测量，在所有年龄段都不容易获得或可行。先前证明直肠器官形态分析（ROMA）基于有明显的表型差异来区分有和不具有CF受试者的类器官：与非CF类器官相比，CF器官具有不规则形状，缺乏可见的管腔。当前的研究在CF诊断不确定时进一步探讨了罗姆人的作用。使用先前建立的ROMA方案分析了Organoid形态。计算了两个指数：量化器官圆度的圆形指数和强度比作为量度的量度，以衡量中央管腔的存在。对116名受试者的直肠类器官进行了培养，并与先前研究的189名受试者一起进行了分析。罗姆人几乎完全歧视了CF和非CF。 Roma指数与SCC，胰腺状态和遗传学相关，证明了收敛的有效性。对于根据当前指南进行诊断不确定的病例，Roma提供了其他诊断信息，并提供了24个中18个诊断性ROMA分类（75％）（75％）。ROMA提供了其他信息来支持CF诊断，而SCC和遗传学不足以进行诊断分类。罗姆人是标准化的，可以集中式化，从而使将来纳入诊断工作中，作为在不明确诊断的情况下，作为第一选择生理测定。
Abstract
Diagnosing cystic fibrosis (CF) is not always straightforward, in particular when sweat chloride concentration (SCC) is intermediate and <2 CF-causing CFTR variants are identified. The physiological CFTR assays proposed in the guidelines, nasal potential difference and intestinal current measurement, are not readily available nor feasible at all ages. Rectal organoid morphology analysis (ROMA) was previously shown to discriminate between organoids from subjects with and without CF based on a distinct phenotypical difference: compared with non-CF organoids, CF organoids have an irregular shape and lack a visible lumen. The current study serves to further explore the role of ROMA when a CF diagnosis is inconclusive.Organoid morphology was analysed using the previously established ROMA protocol. Two indices were calculated: the circularity index to quantify the roundness of organoids and the intensity ratio as a measure of the presence of a central lumen.Rectal organoids from 116 subjects were cultured and analysed together with the 189 subjects from the previous study. ROMA almost completely discriminated between CF and non-CF. ROMA indices correlated with SCC, pancreatic status and genetics, demonstrating convergent validity. For cases with an inconclusive diagnosis according to current guidelines, ROMA provided additional diagnostic information, with a diagnostic ROMA classification for 18 of 24 (75%).ROMA provides additional information to support a CF diagnosis when SCC and genetics are insufficient for diagnostic classification. ROMA is standardised and can be centralised, allowing future inclusion in the diagnostic work-up as first-choice physiological assay in case of an unclear diagnosis.