Rectal organoid morphology analysis (ROMA) as a novel physiological assay for diagnostic classification in cystic fibrosis.

IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Thorax Pub Date : 2024-08-19 DOI:10.1136/thorax-2023-220964
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
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Abstract

Background: 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.

Methods: 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.

Results: 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%).

Discussion: 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.

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直肠类器官形态分析(ROMA)作为一种新型生理检测方法,用于囊性纤维化的诊断分类。
背景:囊性纤维化(CF)的诊断并不总是那么简单,尤其是当汗液氯化物浓度(SCC)处于中间值且发现 CFTR 变异时。指南中提出的 CFTR 生理检测方法--鼻电位差和肠电流测量--并非在所有年龄段都可获得或可行。直肠类器官形态分析(ROMA)先前已被证明可根据一个明显的表型差异来区分有无CF患者的类器官:与非CF类器官相比,CF类器官形状不规则且缺乏可见的管腔。目前的研究旨在进一步探讨ROMA在CF诊断不确定时的作用:方法:使用之前制定的 ROMA 方案分析类器官形态。方法:使用之前建立的 ROMA 方案分析器质性组织形态,计算两个指数:圆度指数用于量化器质性组织的圆度,强度比用于衡量是否存在中心管腔:结果:对 116 名受试者的直肠器官组织进行了培养,并与之前研究中的 189 名受试者一起进行了分析。ROMA几乎完全区分了CF和非CF。ROMA指数与SCC、胰腺状态和遗传学相关,显示了趋同有效性。对于根据现行指南无法确定诊断结果的病例,ROMA提供了额外的诊断信息,24例病例中有18例(75%)通过ROMA进行了诊断分类:讨论:当SCC和遗传学不足以进行诊断分类时,ROMA可为CF诊断提供额外信息支持。ROMA是标准化的,可以集中管理,在诊断不明确时可作为首选生理检测方法纳入诊断工作。
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来源期刊
Thorax
Thorax 医学-呼吸系统
CiteScore
16.10
自引率
2.00%
发文量
197
审稿时长
1 months
期刊介绍: Thorax stands as one of the premier respiratory medicine journals globally, featuring clinical and experimental research articles spanning respiratory medicine, pediatrics, immunology, pharmacology, pathology, and surgery. The journal's mission is to publish noteworthy advancements in scientific understanding that are poised to influence clinical practice significantly. This encompasses articles delving into basic and translational mechanisms applicable to clinical material, covering areas such as cell and molecular biology, genetics, epidemiology, and immunology.
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