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Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function.
de Winter-de Groot, Karin M; Janssens, Hettie M; van Uum, Rick T; Dekkers, Johanna F; Berkers, Gitte; Vonk, Annelotte; Kruisselbrink, Evelien; Oppelaar, Hugo; Vries, Robert; Clevers, Hans; Houwen, Roderick H J; Escher, Johanna C; Elias, Sjoerd G; de Jonge, Hugo R; de Rijke, Yolanda B; Tiddens, Harm A W M; van der Ent, Cornelis K; Beekman, Jeffrey M.
Afiliación
  • de Winter-de Groot KM; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Janssens HM; Dept of Pediatric Pulmonology, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands.
  • van Uum RT; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Dekkers JF; Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Berkers G; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Vonk A; Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Kruisselbrink E; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Oppelaar H; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Vries R; Regenerative Medicine Center Utrecht, University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Clevers H; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Houwen RHJ; Regenerative Medicine Center Utrecht, University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Escher JC; Dept of Pediatric Pulmonology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Elias SG; Regenerative Medicine Center Utrecht, University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • de Jonge HR; Hubrecht Organoid Technology (HUB), Utrecht, The Netherlands.
  • de Rijke YB; Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • Tiddens HAWM; Dept of Pediatric Gastroenterology, Wilhelmina Children's Hospital - University Medical Center, Utrecht University, Utrecht, The Netherlands.
  • van der Ent CK; Dept of Pediatric Gastroenterology, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands.
  • Beekman JM; Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, The Netherlands.
Eur Respir J ; 52(3)2018 09.
Article en En | MEDLINE | ID: mdl-30166324
ABSTRACT
Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers of CFTR function in 34 infants diagnosed with CF. Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p<0.001), had more abnormalities on chest computed tomography (p=0.049), and had lower z-scores for maximal expiratory flow at functional residual capacity (p=0.033) when compared to children with high FIS values. FIS significantly correlated with sweat chloride concentration (SCC) and intestinal current measurement (ICM) (r= -0.82 and r=0.70, respectively; both p<0.001). Individual assessment of SCC, ICM and FIS suggested that FIS can help to classify individual disease severity.Thus, stratification by FIS identified subgroups that differed in pulmonary and gastrointestinal outcome parameters. FIS of intestinal organoids correlated well with established CFTR-dependent biomarkers such as SCC and ICM, and performed adequately at group and individual level in this proof-of-concept study.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Insuficiencia Pancreática Exocrina / Organoides / Regulador de Conductancia de Transmembrana de Fibrosis Quística / Fibrosis Quística Tipo de estudio: Prognostic_studies Límite: Female / Humans / Infant / Male Idioma: En Revista: Eur Respir J Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Insuficiencia Pancreática Exocrina / Organoides / Regulador de Conductancia de Transmembrana de Fibrosis Quística / Fibrosis Quística Tipo de estudio: Prognostic_studies Límite: Female / Humans / Infant / Male Idioma: En Revista: Eur Respir J Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos