Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing CFTR mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p<0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.
- cystic fibrosis
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Collaborators Belgian Organoid Project: Hedwige Boboli (CHR Citadelle, Liège, Belgium), Linda Boulanger (University Hospital Leuven, Belgium), Georges Casimir (HUDERF, Brussels, Belgium), Benedicte De Meyere (University Hospital Ghent, Belgium), Elke De Wachter (University Hospital Brussels, Belgium), Danny De Looze (University Hospital Ghent, Belgium), Isabelle Etienne (CHU Erasme, Brussels, Belgium), Laurence Hanssens (HUDERF, Brussels), Christiane Knoop (CHU Erasme, Brussels, Belgium), Monique Lequesne (University Hospital Antwerp, Belgium), Vicky Nowé (GZA St. Vincentius Hospital Antwerp), Dirk Staessen (GZA St. Vincentius Hospital Antwerp), Stephanie Van Biervliet (University Hospital Ghent, Belgium), Eva Van Braeckel (University Hospital Ghent, Belgium), Kim Van Hoorenbeeck (University Hospital Antwerp, Belgium), Eef Vanderhelst (University Hospital Brussels, Belgium), Stijn Verhulst (University Hospital Antwerp, Belgium), Stefanie Vincken (University Hospital Brussels, Belgium).
Contributors Conceptualisation: SC, ASR, FV and KDB. Methodology: SC, ASR, NC, SM, KDB and FV. Recruiting of CF subjects and collection of rectal biopsies: MB, MP, FV and LD. Recruiting of control subjects and collection of rectal biopsies: MB, MP, FV, LD, KA and MF. Culturing the organoids and performing the rectal organoid morphology analysis: SC, EF and ASR. Analysis of the results and figures preparation: SC, ASR, SF and FV. Writing—original draft: SC, ASR and FV. Writing—review and editing: SC, ASR, NC, SF, EF, KA, MF, CV, SM, MB, MP, LD, KDB, FV, HB, LB, GC, BDM, EDW, DDL, IE, LH, CK, ML, VN, DS, SVB, EVB, KVH, EV, SVe, SVi. Supervision: ASR, FV and KDB.
Funding This study was funded by the Belgian CF patients’ association “Mucovereniging/Association Muco”, the Research Grant of the Belgian Society of Paediatrics BVK-SBP 2019, and a grant from the UZ Leuven Fund for Translational Biomedical Research.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.