PLoS ONE (Jan 2012)

Measurements of CFTR-mediated Cl- secretion in human rectal biopsies constitute a robust biomarker for Cystic Fibrosis diagnosis and prognosis.

  • Marisa Sousa,
  • Maria F Servidoni,
  • Adriana M Vinagre,
  • Anabela S Ramalho,
  • Luciana C Bonadia,
  • Verónica Felício,
  • Maria A Ribeiro,
  • Inna Uliyakina,
  • Fernando A Marson,
  • Arthur Kmit,
  • Silvia R Cardoso,
  • José D Ribeiro,
  • Carmen S Bertuzzo,
  • Lisete Sousa,
  • Karl Kunzelmann,
  • Antônio F Ribeiro,
  • Margarida D Amaral

DOI
https://doi.org/10.1371/journal.pone.0047708
Journal volume & issue
Vol. 7, no. 10
p. e47708

Abstract

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BackgroundCystic Fibrosis (CF) is caused by ∼1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl(-)) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases.Methodology/principal findingsTo further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl(-) secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n=51), individuals with clinical CF suspicion (n=49) and age-matched non-CF controls (n=18). Conclusive measurements were obtained for 96% of cases. Patients with "Classic CF", presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl(-) secretion (Conclusions/significanceDetermination of CFTR-mediated Cl(-) secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-)clinical trials of CFTR-modulator therapies.