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

Cystic Fibrosis

Journal

Thorax
ISSN: 1468-3296
Titre abrégé: Thorax
Pays: England
ID NLM: 0417353

Informations de publication

Date de publication:
14 Jul 2024
Historique:
received: 19 09 2023
accepted: 14 04 2024
medline: 15 7 2024
pubmed: 15 7 2024
entrez: 14 7 2024
Statut: aheadofprint

Résumé

Diagnosing cystic fibrosis (CF) is not always straightforward, in particular when sweat chloride concentration (SCC) is intermediate and <2 CF-causing 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.

Sections du résumé

BACKGROUND BACKGROUND
Diagnosing cystic fibrosis (CF) is not always straightforward, in particular when sweat chloride concentration (SCC) is intermediate and <2 CF-causing
METHODS 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 39004507
pii: thorax-2023-220964
doi: 10.1136/thorax-2023-220964
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

Hedwige Boboli (H)
Linda Boulanger (L)
Georges Casimir (G)
Benedicte Demeyere (B)
Elke De Wachter (E)
Danny De Looze (D)
Anja Delporte (A)
Isabelle Etienne (I)
Laurence Hanssens (L)
Christiane Knoop (C)
Monique Lequesne (M)
Vicky Nowé (V)
Ann Raman (A)
Dirk Staessen (D)
Stephanie Van Biervliet (SV)
Eva Van Braeckel (EV)
Kim Van Hoorenbeeck (KV)
Eef Vanderhelst (E)
Stijn Verhulst (S)
Stefanie Vincken (S)

Informations de copyright

© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Senne Cuyx (S)

Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium.
Department of Pediatrics, Pediatric Pulmonology, University Hospitals Leuven, Leuven, Belgium.

Anabela Santo Ramalho (AS)

Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium.

Steffen Fieuws (S)

Interuniversity Center for Biostatistics and Statistical Bioinformatics, KU Leuven, Leuven, Belgium.
Interuniversity Center for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium.

Nikky Corthout (N)

VIB Bio Imaging Core and VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.
Department of Neuroscience, KU Leuven, Leuven, Belgium.

Marijke Proesmans (M)

Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium.
Department of Pediatrics, Pediatric Pulmonology, University Hospitals Leuven, Leuven, Belgium.

Mieke Boon (M)

Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium.
Department of Pediatrics, Pediatric Pulmonology, University Hospitals Leuven, Leuven, Belgium.

Kaline Arnauts (K)

Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Marianne S Carlon (MS)

Center for Molecular Medicine, KU Leuven, Leuven, Belgium.
Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.

Sebastian Munck (S)

VIB Bio Imaging Core and VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.
Department of Neuroscience, KU Leuven, Leuven, Belgium.

Lieven Dupont (L)

Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.
Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.

Kris De Boeck (K)

Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium.
Department of Pediatrics, Pediatric Pulmonology, University Hospitals Leuven, Leuven, Belgium.

François Vermeulen (F)

Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, KU Leuven, Leuven, Belgium francois.vermeulen@uzleuven.be.
Department of Pediatrics, Pediatric Pulmonology, University Hospitals Leuven, Leuven, Belgium.

Classifications MeSH