Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1534
Título: Measurements of CFTR-Mediated Cl- Secretion in Human Rectal Biopsies Constitute a Robust Biomarker for Cystic Fibrosis Diagnosis and Prognosis
Autor: Sousa, Marisa
Servidoni, Maria F.
Vinagre, Adriana M.
Ramalho, Anabela S.
Bonadia, Luciana C.
Felício, Verónica
Ribeiro, Maria A..
Uliyakina, Inna
Marson A, Fernando
Kmit, Arthur
Cardoso, Silvia R.
Ribeiro, José D.
Bertuzzo, Carmen S.
Sousa, Lisete
Kunzelmann, Karl
Ribeiro, Antônio F.
Amaral, Margarida D.
Palavras-chave: Fibrose Quística
CFTR
Doenças Genéticas
Data: Out-2012
Editora: Dominik Hartl, University of Tu¨ bingen, Germany
Citação: PLoS One. 2012;7(10):e47708. doi: 10.1371/journal.pone.0047708. Epub 2012 Oct 17
Resumo: BACKGROUND: Cystic 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 FINDINGS: To 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 (<5%). Individuals with milder CF disease presented residual CFTR-mediated Cl(-) secretion (10-57%) and non-CF controls show CFTR-mediated Cl(-) secretion ≥ 30-35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in "CF suspicion" individuals allowed to confirm CF in 16/49 individuals (33%) and exclude it in 28/49 (57%). Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl(-) secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. CONCLUSIONS/SIGNIFICANCE: Determination 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.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1534
ISSN: 1932-6203
Versão do Editor: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047708
Aparece nas colecções:DGH - Artigos em revistas internacionais

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Sousa et al_2012_PLoSONE_0047708.pdf526,16 kBAdobe PDFVer/Abrir
Sousa et al_PLoSONE_0047708_Suppl_Methods.pdfDados suplementares129,34 kBAdobe PDFVer/Abrir


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